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"researcher": {"href": "https://publications.scilifelab.se/researcher/e0664d5fa4c4449681bf3baeac074584.json"}}], "type": "meta-analysis", "published": "2023-03-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "volume": "55", "issue": "3", "pages": "410-422", "issn-l": "1061-4036"}, "abstract": "Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by \u22652 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.", "doi": "10.1038/s41588-023-01314-0", "pmid": "36914875", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10011137"}, {"db": "pii", "key": "10.1038/s41588-023-01314-0"}], "notes": [], "created": "2023-04-06T13:50:14.193Z", "modified": "2023-04-06T13:50:15.219Z"}, {"entity": "publication", "iuid": "a85b4e387fa944659cfb0c8c1c5b47ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a85b4e387fa944659cfb0c8c1c5b47ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a85b4e387fa944659cfb0c8c1c5b47ad"}}, "title": "Stroke genetics informs drug discovery and risk prediction across ancestries.", "authors": [{"family": "Mishra", 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{"href": "https://publications.scilifelab.se/researcher/0479b794031d4df7bed96340b3470c19.json"}}, {"family": "Rissanen", "given": "Ina L", "initials": "IL"}, {"family": "Strbian", "given": "Daniel", "initials": "D"}, {"family": "Kim", "given": "Young Jin", "initials": "YJ", "orcid": "0000-0002-4132-4437", "researcher": {"href": "https://publications.scilifelab.se/researcher/a35fb5992bad47038fe5b11c7ed3103f.json"}}, {"family": "Chen", "given": "Pei-Hsin", "initials": "PH"}, {"family": "Mayerhofer", "given": "Ernst", "initials": "E", "orcid": "0000-0001-8902-4209", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce3b53243f0e4a6da6b8ac762ab07a8b.json"}}, {"family": "Howson", "given": "Joanna M M", "initials": "JMM", "orcid": "0000-0001-7618-0050", "researcher": {"href": "https://publications.scilifelab.se/researcher/d427fc29d217410fa1d84c0f9e2bf015.json"}}, {"family": "Irvin", "given": "Marguerite R", "initials": "MR"}, {"family": "Adams", "given": "Hieab", 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"orcid": "0000-0003-0677-8158", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5de431c325e40f4adfe13c06cf1e0b9.json"}}, {"family": "Liaw", "given": "Yung-Po", "initials": "YP"}, {"family": "Seshadri", "given": "Sudha", "initials": "S", "orcid": "0000-0001-6135-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/429e370668ec47ce9945bc5262dccbb3.json"}}, {"family": "Fern\u00e1ndez-Cadenas", "given": "Israel", "initials": "I"}, {"family": "Walters", "given": "Robin G", "initials": "RG", "orcid": "0000-0002-9179-0321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36254611faa44b782b76da870e89bd3.json"}}, {"family": "Ruff", "given": "Christian T", "initials": "CT"}, {"family": "Owolabi", "given": "Mayowa O", "initials": "MO", "orcid": "0000-0003-1146-3070", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ad3b2f403a34896a655f9c318af4c17.json"}}, {"family": "Huffman", "given": "Jennifer E", "initials": "JE", "orcid": "0000-0002-9672-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfa4efb5afae47528265d8be0d5e67fd.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec8d00c4b9d43458c5c895b164695d5.json"}}, {"family": "Kamatani", "given": "Yoichiro", "initials": "Y"}, {"family": "Dichgans", "given": "Martin", "initials": "M", "orcid": "0000-0002-0654-387X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f224e973440f6a78a49b54ca35e3a.json"}}, {"family": "Debette", "given": "Stephanie", "initials": "S"}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "611", "issue": "7934", "pages": "115-123", "issn-l": "0028-0836"}, "abstract": "Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.", "doi": "10.1038/s41586-022-05165-3", "pmid": "36180795", "labels": {"National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-022-05165-3"}, {"db": "pmc", "key": "PMC9524349"}], "notes": [], "created": "2022-11-09T14:36:41.202Z", "modified": "2022-11-09T14:37:47.411Z"}, {"entity": "publication", "iuid": "20044ca7f045473daf17863e0344b451", "links": {"self": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451.json"}, "display": {"href": "https://publications.scilifelab.se/publication/20044ca7f045473daf17863e0344b451"}}, "title": "Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.", "authors": [{"family": "Winkler", "given": "Thomas W", "initials": "TW", "orcid": "0000-0003-0292-5421", "researcher": {"href": "https://publications.scilifelab.se/researcher/613c02e5736a4357bcfff184bebb714e.json"}}, {"family": "Rasheed", "given": "Humaira", "initials": "H", "orcid": "0000-0002-3331-5864", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfbae7ea55074f9292e48aaf6d815a03.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Gorski", "given": "Mathias", "initials": "M"}, {"family": "Rowan", "given": "Bryce X", "initials": "BX"}, {"family": "Stanzick", "given": "Kira J", "initials": "KJ"}, {"family": "Thomas", "given": "Laurent F", "initials": "LF"}, {"family": "Tin", "given": "Adrienne", "initials": "A", "orcid": "0000-0002-4207-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c33ed3b64348be904a14698402445e.json"}}, {"family": "Hoppmann", "given": "Anselm", "initials": "A"}, {"family": "Chu", "given": "Audrey Y", "initials": "AY"}, {"family": "Tayo", "given": "Bamidele", "initials": "B"}, {"family": "Thio", "given": "Chris H L", "initials": "CHL"}, {"family": "Cusi", "given": "Daniele", "initials": "D"}, {"family": "Chai", "given": "Jin-Fang", "initials": "JF"}, {"family": "Sieber", "given": "Karsten B", "initials": "KB"}, {"family": "Horn", "given": "Katrin", "initials": "K"}, {"family": "Li", "given": "Man", "initials": "M"}, {"family": "Scholz", "given": "Markus", "initials": "M"}, {"family": "Cocca", "given": "Massimiliano", "initials": "M", "orcid": "0000-0002-1127-7596", "researcher": {"href": "https://publications.scilifelab.se/researcher/86431d25a54645e3988674b5e0ef6a59.json"}}, {"family": "Wuttke", "given": "Matthias", "initials": "M"}, {"family": "van der Most", "given": "Peter J", "initials": "PJ", 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"https://publications.scilifelab.se/researcher/34990140a9604dd7b61807dafc8fabc6.json"}}], "type": "journal article", "published": "2022-06-13", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "5", "issue": "1", "pages": "580", "issn-l": "2399-3642"}, "abstract": "Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.", "doi": "10.1038/s42003-022-03448-z", "pmid": "35697829", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-022-03448-z"}, {"db": "pmc", "key": "PMC9192715"}], "notes": [], "created": "2022-06-14T13:16:22.813Z", "modified": "2022-11-21T15:40:40.440Z"}, {"entity": "publication", "iuid": "e389be71822d45d6ac04d848bfb48df6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e389be71822d45d6ac04d848bfb48df6"}}, "title": "The power of genetic diversity in genome-wide association studies of lipids.", "authors": [{"family": "Graham", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-1271-2489", 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"https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Sun", "given": "Yan V", "initials": "YV", "orcid": "0000-0002-2838-1824", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6299caf6b6342fdbfab4c0d9738b28f.json"}}, {"family": "Willer", "given": "Cristen J", "initials": "CJ", "orcid": "0000-0001-5645-4966", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a8e1d33146452b87e7e21eb5339f80.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "600", "issue": "7890", "pages": "675-679", "issn-l": "0028-0836"}, "abstract": "Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.", "doi": "10.1038/s41586-021-04064-3", "pmid": "34887591", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1758809"}, {"db": "pmc", "key": "PMC8730582"}, {"db": "pii", "key": "10.1038/s41586-021-04064-3"}], "notes": [], "created": "2021-12-22T19:39:50.082Z", "modified": "2023-06-19T12:31:07.699Z"}, {"entity": "publication", "iuid": "48f74c2afc0b4af8befb22016e4d7b0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48f74c2afc0b4af8befb22016e4d7b0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/48f74c2afc0b4af8befb22016e4d7b0c"}}, "title": "Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.", "authors": [{"family": "Lagou", "given": "Vasiliki", "initials": "V"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Hottenga", "given": "Jouke- Jan", "initials": "JJ", "orcid": "0000-0002-5668-2368", "researcher": {"href": "https://publications.scilifelab.se/researcher/75553b594b1f4255833de730f7f7d170.json"}}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Perry", "given": "John R B", "initials": "JRB"}, {"family": "Bouatia-Naji", "given": "Nabila", "initials": "N", "orcid": "0000-0001-5424-2134", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4f7af2cb2b7464abddf05692a292fc3.json"}}, {"family": "Marullo", "given": "Letizia", "initials": "L"}, {"family": "Rybin", "given": "Denis", "initials": "D"}, {"family": "Jansen", "given": "Rick", "initials": "R", "orcid": "0000-0002-3333-6737", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcd392c9b9784ebe8c8730e05463377a.json"}}, {"family": "Min", "given": "Josine L", "initials": "JL", "orcid": "0000-0003-4456-9824", "researcher": {"href": "https://publications.scilifelab.se/researcher/5896cbc0cb8d427a954b194839adda52.json"}}, {"family": "Dimas", "given": "Antigone S", "initials": "AS"}, {"family": "Ulrich", "given": "Anna", "initials": "A"}, {"family": "Zudina", "given": "Liudmila", "initials": "L"}, {"family": "G\u00e5din", "given": "Jesper R", "initials": "JR"}, {"family": "Jiang", "given": "Longda", "initials": "L"}, {"family": "Faggian", "given": "Alessia", "initials": "A", "orcid": "0000-0002-3799-9722", "researcher": {"href": "https://publications.scilifelab.se/researcher/e4f320f96474406c82fef88f1f78dd23.json"}}, {"family": "Bonnefond", "given": "Am\u00e9lie", "initials": "A", "orcid": "0000-0001-9976-3005", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea1984308c1544ba969d4df73971de69.json"}}, {"family": "Fadista", "given": "Joao", "initials": "J"}, {"family": "Stathopoulou", "given": "Maria G", "initials": "MG"}, {"family": "Isaacs", "given": "Aaron", "initials": "A", "orcid": "0000-0001-5037-4834", "researcher": {"href": "https://publications.scilifelab.se/researcher/38ebe49e62404f48bcb979d9671883e7.json"}}, {"family": "Willems", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-6803-3007", "researcher": {"href": "https://publications.scilifelab.se/researcher/307c8a9b3ab54ab586c7b000c110e76b.json"}}, {"family": "Navarro", "given": "Pau", "initials": "P", "orcid": "0000-0001-5576-8584", "researcher": {"href": "https://publications.scilifelab.se/researcher/9420946aedec4a7b8925cc05c0a9abeb.json"}}, {"family": "Tanaka", "given": "Toshiko", "initials": "T"}, {"family": "Jackson", "given": "Anne U", "initials": "AU", "orcid": "0000-0002-9672-2547", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8230afabb0b4dcda8dc58ead349aea0.json"}}, {"family": "Montasser", "given": "May E", "initials": "ME"}, {"family": "O'Connell", "given": "Jeff R", "initials": "JR"}, {"family": "Bielak", "given": "Lawrence F", "initials": "LF", "orcid": "0000-0002-3443-8030", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1934e3543f14cbe83b95d1c1c3e24c7.json"}}, {"family": "Webster", "given": "Rebecca J", "initials": "RJ"}, {"family": "Saxena", "given": "Richa", "initials": "R", "orcid": "0000-0003-2233-1065", "researcher": {"href": "https://publications.scilifelab.se/researcher/a974c0165c8c4e79b5773f98dcd2ce0e.json"}}, {"family": "Stafford", "given": "Jeanette M", "initials": "JM"}, {"family": "Pourcain", "given": "Beate St", "initials": "BS"}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ"}, {"family": "Salo", "given": "Perttu", "initials": "P"}, {"family": "Shin", "given": "So-Youn", "initials": "SY"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Smith", "given": "Albert V", "initials": "AV", "orcid": "0000-0003-1942-5845", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b28739aa7d746718d670363d7c18a40.json"}}, {"family": "Li", "given": "Guo", "initials": "G"}, {"family": "Verweij", "given": "Niek", "initials": "N", "orcid": "0000-0002-4303-7685", "researcher": {"href": "https://publications.scilifelab.se/researcher/7306319d42a640a483b937de588a17a4.json"}}, {"family": "Goel", "given": "Anuj", "initials": "A", "orcid": "0000-0003-2307-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f16d9d2e2164938a12b027326c21316.json"}}, {"family": "Ford", "given": "Ian", "initials": "I"}, {"family": "Johnson", "given": "Paul C D", "initials": "PCD", "orcid": "0000-0001-6663-7520", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d7b476aaf134a44862c87b7a6e6ee27.json"}}, {"family": "Johnson", "given": "Toby", 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{"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V", "orcid": "0000-0003-3423-2021", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c95879213664e00b66aeee2e8ece975.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "Silbernagel", "given": "G\u00fcnther", "initials": "G"}, {"family": "Meyer", "given": "Julia", "initials": "J"}, {"family": "M\u00fcller-Nurasyid", "given": "Martina", "initials": "M", "orcid": "0000-0003-3793-5910", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d21299bb41343f88142255e64a9da57.json"}}, {"family": "Ganna", "given": "Andrea", 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"given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "MR", "orcid": "0000-0002-2149-0630", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7d00b649d284101b0501e2024fb651a.json"}}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Nicholson", "given": "George", "initials": "G"}, {"family": "Karpe", "given": "Fredrik", "initials": "F"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET", "orcid": "0000-0002-9302-6490", "researcher": {"href": "https://publications.scilifelab.se/researcher/3560d19929e94af1bb858a54e29a10cc.json"}}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM", "orcid": "0000-0002-4903-9374", "researcher": {"href": "https://publications.scilifelab.se/researcher/822d2f2a99814a7498f19976ed6381ef.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Froguel", "given": "Philippe", "initials": "P", "orcid": "0000-0003-2972-0784", "researcher": {"href": "https://publications.scilifelab.se/researcher/34edc6a0f1b343bb8a2abd439c2ee77f.json"}}, {"family": "Kaakinen", "given": "Marika A", "initials": "MA", "orcid": "0000-0002-9228-0462", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9f40717fdd4ce29b148bc569134451.json"}}, {"family": "Lyssenko", "given": "Valeriya", "initials": "V"}, {"family": "Watanabe", "given": "Richard M", "initials": "RM", "orcid": "0000-0003-1015-0531", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4336f8845ac40dfb77ef0ea1a97bbd6.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E", "orcid": "0000-0003-2256-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/689bc741ea6547d18de7080c84d0193e.json"}}, {"family": "Florez", "given": "Jose C", "initials": "JC"}, {"family": "Dupuis", "given": "Jos\u00e9e", "initials": "J", "orcid": "0000-0003-2871-3603", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9edfafda7364890866115f5343a9583.json"}}, {"family": "Barroso", "given": "In\u00eas", "initials": "I", "orcid": "0000-0001-5800-4520", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2dc6be9aa194bdc9a161e551d5e6747.json"}}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Prokopenko", "given": "Inga", "initials": "I"}, {"family": "Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)", "given": "", "initials": ""}], "type": "journal article", "published": "2021-01-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "24", "issn-l": "2041-1723"}, "abstract": "Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.", "doi": "10.1038/s41467-020-19366-9", "pmid": "33402679", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": null, "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-19366-9"}, {"db": "pmc", "key": "PMC7785747"}], "notes": [], "created": "2021-01-08T16:30:26.062Z", "modified": "2021-11-10T12:27:48.827Z"}, {"entity": "publication", "iuid": "06bdda0e02974b29a11b5fc22fa91b3b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b"}}, "title": "Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.", "authors": [{"family": "van Zuydam", "given": "Natalie R", "initials": "NR", "orcid": "0000-0002-9809-1398", "researcher": {"href": "https://publications.scilifelab.se/researcher/defa68cc40734fcdaffd7ba0aaad72b8.json"}}, {"family": "Ladenvall", "given": "Claes", "initials": "C", "orcid": "0000-0002-7501-6598", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5c362dc308476195eb55d2e588ba60.json"}}, {"family": "Voight", "given": "Benjamin F", "initials": "BF", "orcid": "0000-0002-6205-9994", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d9e9de96ee4983ba97efc14eb3d79b.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Fernandez-Tajes", "given": "Juan", "initials": "J", "orcid": "0000-0003-1515-2421", "researcher": {"href": "https://publications.scilifelab.se/researcher/dad51251fc8d42f793e4c991c4102667.json"}}, {"family": "Rayner", "given": "N William", "initials": "NW", "orcid": "0000-0003-0510-4792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e3c7e5bd20348629ba3fe232fc2bcd2.json"}}, {"family": "Robertson", "given": "Neil R", "initials": "NR"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Vlachopoulou", "given": "Efthymia", "initials": "E"}, {"family": "Goel", "given": "Anuj", "initials": "A", "orcid": "0000-0003-2307-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f16d9d2e2164938a12b027326c21316.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Kwee", "given": "Lydia Coulter", "initials": "LC", "orcid": "0000-0002-6997-8571", "researcher": {"href": 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"https://publications.scilifelab.se/researcher/6fde24cdfda24aed83d888da0d9b6811.json"}}, {"family": "Salomaa", "given": "Veikko", "initials": "V", "orcid": "0000-0001-7563-5324", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2396c578c254e39b66538c3033c9ce9.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Watkins", "given": "Hugh", "initials": "H", "orcid": "0000-0002-5287-9016", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea10989397546f9a027f88bd491bb8b.json"}}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Colhoun", "given": "Helen M", "initials": "HM", "orcid": "0000-0002-8345-3288", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79cb60e3d734232b7cfad20c4f1c13e.json"}}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Circ Genom Precis Med", "issn": "2574-8300", "issn-l": "2574-8300", "volume": "13", "issue": "6", "pages": "e002769"}, "abstract": "Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).\r\n\r\nTo test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).\r\n\r\nNone of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.\r\n\r\nThis study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.", "doi": "10.1161/CIRCGEN.119.002769", "pmid": "33321069", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7748049"}], "notes": [], "created": "2021-01-07T17:01:51.462Z", "modified": "2021-12-07T13:47:48.005Z"}, {"entity": "publication", "iuid": "d98c58bf1e6e4de9b468b52b6592fa41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d98c58bf1e6e4de9b468b52b6592fa41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d98c58bf1e6e4de9b468b52b6592fa41"}}, "title": "Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.", "authors": [{"family": "Ntalla", "given": "Ioanna", "initials": "I"}, {"family": "Weng", "given": "Lu-Chen", "initials": "LC", "orcid": "0000-0003-1475-4930", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e52c9c21794412bbb3750fda1fecfe0.json"}}, {"family": "Cartwright", "given": "James H", "initials": "JH"}, {"family": "Hall", "given": "Amelia Weber", "initials": "AW", "orcid": "0000-0002-7915-0313", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a151b393a6c434585d4834fd32de6a4.json"}}, {"family": "Sveinbjornsson", "given": "Gardar", "initials": "G"}, {"family": "Tucker", "given": "Nathan R", "initials": "NR", "orcid": "0000-0002-5071-4218", "researcher": {"href": "https://publications.scilifelab.se/researcher/f89b1366ff014dc6a9cc5fe4bd37becf.json"}}, {"family": "Choi", "given": "Seung Hoan", "initials": "SH"}, {"family": "Chaffin", "given": "Mark D", "initials": "MD", "orcid": "0000-0002-1234-5562", "researcher": {"href": "https://publications.scilifelab.se/researcher/c73477de5ca0468ab051fd6eab7bad81.json"}}, {"family": "Roselli", "given": "Carolina", "initials": "C", "orcid": "0000-0001-5267-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dd28aad250f42719d505c21ed76013b.json"}}, {"family": "Barnes", "given": "Michael R", "initials": "MR", "orcid": "0000-0001-9097-7381", "researcher": {"href": "https://publications.scilifelab.se/researcher/bffbcdd5aad340b98d7da297ffc21e6b.json"}}, {"family": "Mifsud", "given": "Borbala", "initials": "B", "orcid": "0000-0003-3429-3094", "researcher": {"href": "https://publications.scilifelab.se/researcher/0105dc446d594b0bb3be38b8eb94a16b.json"}}, {"family": "Warren", "given": "Helen R", "initials": "HR"}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": 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{"family": "Launer", "given": "Lenore J", "initials": "LJ"}, {"family": "Smith", "given": "Albert V", "initials": "AV", "orcid": "0000-0003-1942-5845", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b28739aa7d746718d670363d7c18a40.json"}}, {"family": "Bottinger", "given": "Erwin P", "initials": "EP"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5b6c24c302d42828806076ded81afe1.json"}}, {"family": "Nadkarni", "given": "Girish N", "initials": "GN"}, {"family": "Preuss", "given": "Michael H", "initials": "MH", "orcid": "0000-0001-5266-8465", "researcher": {"href": "https://publications.scilifelab.se/researcher/15cc6eb5d229484bae01b80781eae224.json"}}, {"family": "Correa", "given": "Adolfo", "initials": "A", "orcid": "0000-0002-9501-600X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a12b716143c4156b060f87d5373b87d.json"}}, 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"https://publications.scilifelab.se/researcher/9d897d8376084cc8905fa9177803ecba.json"}}, {"family": "Yldau van der Ende", "given": "M", "initials": "M"}, {"family": "Lambiase", "given": "Pier D", "initials": "PD"}, {"family": "Orini", "given": "Michele", "initials": "M", "orcid": "0000-0001-5773-0344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad2b6285769e43d59eaa61068cd9307d.json"}}, {"family": "Ramirez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4130-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff795d161ab5418ebbb32c64fc9628cf.json"}}, {"family": "Van Duijvenboden", "given": "Stefan", "initials": "S", "orcid": "0000-0001-8897-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bedcb22e237147019c8a97c32e164456.json"}}, {"family": "Arnar", "given": "David O", "initials": "DO"}, {"family": "Gudbjartsson", "given": "Daniel F", "initials": "DF", "orcid": "0000-0002-5222-9857", "researcher": {"href": "https://publications.scilifelab.se/researcher/e41ffdc303534408aade6e4a071e4801.json"}}, {"family": "Holm", "given": "Hilma", "initials": "H"}, {"family": "Sulem", "given": "Patrick", "initials": "P", "orcid": "0000-0001-7123-6123", "researcher": {"href": "https://publications.scilifelab.se/researcher/a228963aa2c148ee82e526d07e298364.json"}}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "Thorolfsdottir", "given": "Rosa B", "initials": "RB", "orcid": "0000-0001-7475-0398", "researcher": {"href": "https://publications.scilifelab.se/researcher/e803af5742504636a2d16ae252f94af4.json"}}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Benjamin", "given": "Emelia J", "initials": "EJ", "orcid": "0000-0003-4076-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/31c69bdf118d4b36ad65a6c4f780bab2.json"}}, {"family": "Tinker", "given": "Andrew", "initials": "A"}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd513dc49e0945bc8298f72d1244648d.json"}}, {"family": "Jamshidi", "given": "Yalda", "initials": "Y", "orcid": "0000-0003-0151-6482", "researcher": {"href": "https://publications.scilifelab.se/researcher/66a90ee88cbf4e9b9e782548fe4991c0.json"}}, {"family": "Lubitz", "given": "Steven A", "initials": "SA", "orcid": "0000-0002-9599-4866", "researcher": {"href": "https://publications.scilifelab.se/researcher/25bb007311104c92983dbcce80f72260.json"}}, {"family": "Munroe", "given": "Patricia B", "initials": "PB", "orcid": "0000-0002-4176-2947", "researcher": {"href": "https://publications.scilifelab.se/researcher/657544a7f921459f926aae5cd0e2065c.json"}}], "type": "journal article", "published": "2020-05-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "2542", "issn-l": "2041-1723"}, "abstract": "The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.", "doi": "10.1038/s41467-020-15706-x", "pmid": "32439900", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15706-x"}, {"db": "pmc", "key": "PMC7242331"}], "notes": [], "created": "2020-05-27T13:29:26.954Z", "modified": "2021-11-10T12:50:53.503Z"}, {"entity": "publication", "iuid": "7ece5c90f5a84512a7eef65aed76aed2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2"}}, "title": "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.", "authors": [{"family": "Shah", "given": "Sonia", "initials": "S", "orcid": "0000-0001-5860-4526", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6a8568b3cae476199b27818eeb19e4d.json"}}, {"family": "Henry", "given": "Albert", "initials": "A", "orcid": "0000-0001-7422-2288", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b1557b87fc542eb8e4d7b733e5b79dc.json"}}, {"family": "Roselli", "given": "Carolina", "initials": "C", "orcid": "0000-0001-5267-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dd28aad250f42719d505c21ed76013b.json"}}, {"family": "Lin", "given": "Honghuang", "initials": "H", "orcid": "0000-0003-3043-3942", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bc2f1e6bb1140dfa054376eac685d5e.json"}}, {"family": "Sveinbj\u00f6rnsson", "given": "Gar\u00f0ar", "initials": "G"}, {"family": "Fatemifar", "given": "Ghazaleh", "initials": "G"}, {"family": "Hedman", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Wilk", "given": "Jemma B", "initials": "JB"}, {"family": "Morley", "given": "Michael P", "initials": "MP"}, {"family": "Chaffin", "given": "Mark D", "initials": "MD", "orcid": "0000-0002-1234-5562", "researcher": {"href": "https://publications.scilifelab.se/researcher/c73477de5ca0468ab051fd6eab7bad81.json"}}, {"family": "Helgadottir", "given": "Anna", "initials": "A", "orcid": "0000-0002-1806-2467", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b5de2b760674dbfba05df40af0eb38f.json"}}, {"family": "Verweij", "given": "Niek", "initials": "N", "orcid": "0000-0002-4303-7685", "researcher": {"href": "https://publications.scilifelab.se/researcher/7306319d42a640a483b937de588a17a4.json"}}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Almgren", "given": "Peter", "initials": "P", "orcid": "0000-0002-0473-0241", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c1a61189c4846eaa1de74d1fd79c8bb.json"}}, {"family": "Andersson", "given": "Charlotte", "initials": "C"}, {"family": "Aragam", "given": "Krishna G", "initials": "KG"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Backman", "given": "Joshua D", "initials": "JD"}, {"family": "Biggs", "given": "Mary L", "initials": "ML"}, {"family": "Bloom", "given": "Heather L", "initials": "HL"}, {"family": "Brandimarto", "given": "Jeffrey", "initials": "J"}, {"family": "Brown", "given": "Michael R", "initials": "MR"}, {"family": "Buckbinder", "given": "Leonard", "initials": "L"}, {"family": "Carey", "given": "David J", "initials": "DJ"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Chen", "given": "Xing", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d354d5ca83c4059b8151c8e67b99405.json"}}, {"family": "Chen", "given": "Xu", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": 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{"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Cappola", "given": "Thomas P", "initials": "TP", "orcid": "0000-0002-9630-7204", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cc50d241ad14477b91f83e012918181.json"}}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "Kuchenbaecker", "given": "Karoline", "initials": "K", "orcid": "0000-0001-9726-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e142157c79648ce96b258ea78019829.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd513dc49e0945bc8298f72d1244648d.json"}}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Vasan", "given": "Ramachandran S", "initials": "RS", "orcid": "0000-0001-7357-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/50ceef6f00ea4251a5e1e83cd379a506.json"}}, {"family": "Swerdlow", "given": "Daniel I", "initials": "DI"}, {"family": "Lumbers", "given": "R Thomas", "initials": "RT", "orcid": "0000-0002-9077-4741", "researcher": {"href": "https://publications.scilifelab.se/researcher/a53e4d6591db481f881ec6046d54535b.json"}}], "type": "journal article", "published": "2020-01-09", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "163", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.", "doi": "10.1038/s41467-019-13690-5", "pmid": "31919418", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6952380"}, {"db": "pii", "key": "10.1038/s41467-019-13690-5"}], "notes": [], "created": "2020-01-14T10:04:57.921Z", "modified": "2023-06-19T13:01:57.741Z"}, {"entity": "publication", "iuid": "89c87476555544e39ef6bf6717603f84", "links": {"self": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84.json"}, "display": {"href": "https://publications.scilifelab.se/publication/89c87476555544e39ef6bf6717603f84"}}, "title": "Associations of autozygosity with a broad range of human phenotypes.", "authors": [{"family": "Clark", "given": "David W", "initials": "DW", "orcid": "0000-0002-1025-9185", "researcher": {"href": 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"initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}, {"family": "Rotimi", "given": "Charles", "initials": "C", "orcid": "0000-0001-5759-053X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fa2951fdebf4fddaad296d49b8f3f2b.json"}}, {"family": "Rotter", "given": "Jerome I", "initials": "JI", "orcid": "0000-0001-7191-1723", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9bdbf58ae94fc8b455bbbcbcaa50ce.json"}}, {"family": "Rudan", "given": "Igor", "initials": "I", "orcid": "0000-0001-6993-6884", "researcher": {"href": "https://publications.scilifelab.se/researcher/d50e1ca836e841f8a7a748ae93b59d75.json"}}, {"family": "Den Ruijter", "given": "Hester M", "initials": "HM"}, {"family": "Sanghera", "given": "Dharambir K", "initials": "DK"}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Schmidt", "given": "Reinhold", "initials": "R"}, {"family": "Schulze", "given": "Matthias B", "initials": "MB"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Scott", "given": "Robert A", "initials": "RA"}, {"family": "Shuldiner", "given": "Alan R", "initials": "AR"}, {"family": "Sim", "given": "Xueling", "initials": "X", "orcid": "0000-0002-1233-7642", "researcher": {"href": "https://publications.scilifelab.se/researcher/3216a8d2a7264a1390a886fa09d5d648.json"}}, {"family": "Small", "given": "Neil", "initials": "N"}, {"family": "Smith", "given": "Jennifer A", "initials": "JA", "orcid": "0000-0002-3575-5468", "researcher": {"href": "https://publications.scilifelab.se/researcher/311c7381092b4143bcd2e4ef93250526.json"}}, {"family": "Sotoodehnia", "given": "Nona", "initials": "N"}, {"family": "Tai", "given": "E-Shyong", "initials": "ES"}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0002-7141-9189", "researcher": {"href": "https://publications.scilifelab.se/researcher/764ab7a82db24557a5de0fad97bf53f3.json"}}, {"family": "Toniolo", "given": "Daniela", "initials": "D"}, {"family": "Tregouet", "given": "David-Alexandre", "initials": "DA"}, {"family": "Tuomi", "given": "Tiinamaija", "initials": "T", "orcid": "0000-0002-8306-6202", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f5ce9936ca454c85f0af966acac5c0.json"}}, {"family": "Vollenweider", "given": "Peter", "initials": "P"}, {"family": "Wang", "given": "Carol A", "initials": "CA", "orcid": "0000-0002-4301-3974", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf99a43c27034a68976e978b104a91d7.json"}}, {"family": "Weir", "given": "David R", "initials": "DR", "orcid": "0000-0002-1661-2402", "researcher": {"href": "https://publications.scilifelab.se/researcher/f90b7cfe829845fb8cbea9558a5c82a7.json"}}, {"family": "Whitfield", "given": "John B", "initials": "JB", "orcid": "0000-0002-1103-0876", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0f61a914f9748ee9047301da8026bd7.json"}}, {"family": "Wijmenga", "given": "Cisca", "initials": "C"}, {"family": "Wong", "given": "Tien-Yin", "initials": "TY"}, {"family": "Wright", "given": "John", "initials": "J"}, {"family": "Yang", "given": "Jingyun", "initials": "J"}, {"family": "Yu", "given": "Lei", "initials": "L"}, {"family": "Zemel", "given": "Babette S", "initials": "BS"}, {"family": "Zonderman", "given": "Alan B", "initials": "AB"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5b6c24c302d42828806076ded81afe1.json"}}, {"family": "Franceschini", "given": "Nora", "initials": "N"}, {"family": "Franke", "given": "Lude", "initials": "L", "orcid": "0000-0002-5159-8802", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee63161f78274a53b615c05555b81a10.json"}}, {"family": "Haley", "given": "Chris S", "initials": "CS", "orcid": "0000-0002-9811-0210", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4fee769cfe84186abbc285881e0529c.json"}}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": "Walters", "given": "Robin G", "initials": "RG", "orcid": "0000-0002-9179-0321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36254611faa44b782b76da870e89bd3.json"}}, {"family": "Perry", "given": "John R B", "initials": "JRB"}, {"family": "Esko", "given": "T\u014dnu", "initials": "T"}, {"family": "Helgason", "given": "Agnar", "initials": "A"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Joshi", "given": "Peter K", "initials": "PK", "orcid": "0000-0002-6361-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/46050ddec8f64054b3bab46c5016aebf.json"}}, {"family": "Kubo", "given": "Michiaki", "initials": "M"}, {"family": "Wilson", "given": "James F", "initials": "JF", "orcid": "0000-0001-5751-9178", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39e6e0f7210494cb4f80be0f7413b6f.json"}}], "type": "journal article", "published": "2019-10-31", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "4957", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.", "doi": "10.1038/s41467-019-12283-6", "pmid": "31673082", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6823371"}, {"db": "pii", "key": "10.1038/s41467-019-12283-6"}], "notes": [], "created": "2019-11-28T07:41:34.797Z", "modified": "2023-06-19T13:09:10.356Z"}, {"entity": "publication", "iuid": "a212f36b24ed408086fd6d1b5ab1eab5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a212f36b24ed408086fd6d1b5ab1eab5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a212f36b24ed408086fd6d1b5ab1eab5"}}, "title": "A catalog of genetic loci associated with kidney function from analyses of a million individuals.", "authors": [{"family": "Wuttke", "given": "Matthias", "initials": "M", "orcid": 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"https://publications.scilifelab.se/researcher/df3f5b6e8cb7470c880cff6dc960f283.json"}}, {"family": "Heid", "given": "Iris M", "initials": "IM"}, {"family": "Scholz", "given": "Markus", "initials": "M", "orcid": "0000-0002-4059-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d7b0e2dcdb4361b54016cb1550c5fe.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "K\u00f6ttgen", "given": "Anna", "initials": "A", "orcid": "0000-0002-4671-3714", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4cb85a14da4db6bc932a8bc4148efb.json"}}, {"family": "Pattaro", "given": "Cristian", "initials": "C", "orcid": "0000-0002-4119-0109", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a6a570bbec647b188c4a7a5da03caac.json"}}], "type": "journal article", "published": "2019-06-00", "journal": {"volume": "51", "issn": "1546-1718", "issue": "6", "pages": "957-972", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.", "doi": "10.1038/s41588-019-0407-x", "pmid": "31152163", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-019-0407-x"}, {"db": "pmc", "key": "PMC6698888"}, {"db": "mid", "key": "NIHMS1038587"}], "notes": [], "created": "2019-06-04T12:49:02.356Z", "modified": "2021-06-21T11:50:41.587Z"}]}