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"David P", "initials": "DP", "orcid": "0000-0001-7854-1366", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f96a3bb72be4068ad3c3200bf75e50a.json"}}, {"family": "Walters", "given": "Robin G", "initials": "RG", "orcid": "0000-0002-9179-0321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36254611faa44b782b76da870e89bd3.json"}}, {"family": "Morris", "given": "Andrew P", "initials": "AP", "orcid": "0000-0002-6805-6014", "researcher": {"href": "https://publications.scilifelab.se/researcher/991fd686a4a040a1a197c1f32d5b731b.json"}}, {"family": "London", "given": "Stephanie J", "initials": "SJ", "orcid": "0000-0003-4911-5290", "researcher": {"href": "https://publications.scilifelab.se/researcher/7542ea2dd880470b8f3330e8b74eeb5c.json"}}, {"family": "Cho", "given": "Michael H", "initials": "MH", "orcid": "0000-0002-4907-1657", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa377da2fe604b18babe1ab6475ad942.json"}}, {"family": "Wain", "given": "Louise V", "initials": "LV", "orcid": "0000-0003-4951-1867", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5ac36354ef94bafa622965e847cbae7.json"}}, {"family": "Hall", "given": "Ian P", "initials": "IP", "orcid": "0000-0001-9933-3216", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a31b8b1ed6d42abb9a64b387bb0a414.json"}}, {"family": "Tobin", "given": "Martin D", "initials": "MD", "orcid": "0000-0002-3596-7874", "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", "initials": "H", "orcid": "0000-0003-3687-2508", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab5c4744d60d4290a3a8a6b80c107f42.json"}}, {"family": "Wassertheil-Smoller", "given": "Sylvia", "initials": "S", "orcid": "0000-0002-5447-4653", "researcher": {"href": "https://publications.scilifelab.se/researcher/d091e3704a9948209449f28c974181a8.json"}}, {"family": "Christensen", "given": "Kaare", "initials": "K", "orcid": "0000-0002-5429-5292", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79ea43d09544efc95351b52ac682910.json"}}, {"family": "Ikram", "given": "Mohammad A", "initials": "MA", "orcid": "0000-0003-0372-8585", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ec81571f4a94af682b4e23526f87385.json"}}, {"family": "Rundek", "given": "Tatjana", "initials": "T", "orcid": "0000-0002-7115-9815", "researcher": {"href": "https://publications.scilifelab.se/researcher/34ebc54256244a76a59f4eef9540522c.json"}}, {"family": "Worrall", "given": "Bradford B", "initials": "BB", "orcid": "0000-0001-9386-4091", "researcher": {"href": "https://publications.scilifelab.se/researcher/159cc0760bf542129d186e25dfde87bc.json"}}, {"family": "Lathrop", "given": "G Mark", "initials": "GM"}, {"family": "Riaz", "given": "Moeen", "initials": "M"}, {"family": "Simonsick", "given": "Eleanor M", "initials": "EM"}, {"family": "K\u00f5rv", "given": "Janika", "initials": "J", "orcid": "0000-0002-6074-0727", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9943be062e54db085c24868a871404f.json"}}, {"family": "Fran\u00e7a", "given": "Paulo H C", "initials": "PHC", "orcid": "0000-0002-1750-9132", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3c1d16b0e54523b12c12e52f245fda.json"}}, {"family": "Zand", "given": "Ramin", "initials": "R"}, {"family": "Prasad", "given": "Kameshwar", "initials": "K"}, {"family": "Frikke-Schmidt", "given": "Ruth", "initials": "R", "orcid": 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"0000-0002-6795-4760", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e23d12d8f5340a79e86a293593c9598.json"}}, {"family": "Damrauer", "given": "Scott M", "initials": "SM"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI", "orcid": "0000-0003-3357-0862", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c06690291064fe58836958edbcaafbc.json"}}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Anderson", "given": "Christopher D", "initials": "CD"}, {"family": "Zwart", "given": "John-Anker", "initials": "JA", "orcid": "0000-0001-5721-0154", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6ba64e625064349b7405b23439e1bfe.json"}}, {"family": "Niiranen", "given": "Teemu J", "initials": "TJ", "orcid": "0000-0002-7394-7487", "researcher": {"href": "https://publications.scilifelab.se/researcher/d52ad3773441442fbad63cbe33959735.json"}}, {"family": "Fornage", "given": "Myriam", "initials": "M", "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": "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", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e302d0cabab449caf7efca024e6d627.json"}}, {"family": "Clarke", "given": "Shoa L", "initials": "SL", "orcid": "0000-0002-6592-1172", "researcher": {"href": "https://publications.scilifelab.se/researcher/91e526cf78cf4323b8625e5bfe7728e1.json"}}, {"family": "Wu", "given": "Kuan-Han H", "initials": "KH", "orcid": "0000-0003-4286-4299", "researcher": {"href": "https://publications.scilifelab.se/researcher/44072ea2199c47d9a24c368b90439a06.json"}}, {"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Zajac", "given": "Greg J M", "initials": "GJM", "orcid": "0000-0001-6411-9666", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a903723e08040f5b9eb0086fdcbdcd2.json"}}, {"family": "Ramdas", "given": "Shweta", "initials": 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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": "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": "https://publications.scilifelab.se/researcher/a71ee9badf4f458d9b04ebf89f5f16c9.json"}}, {"family": "Okada", "given": "Yukinori", "initials": "Y", "orcid": "0000-0002-0311-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/40b13860bfef41959c29be2de853b456.json"}}, {"family": "Moore", "given": "Kristjan H S", "initials": "KHS", "orcid": "0000-0002-9579-4362", "researcher": {"href": "https://publications.scilifelab.se/researcher/38a8eaf6f23c4dd9a90cda85b0a998b5.json"}}, {"family": "Mason", "given": "Dan", "initials": "D", "orcid": "0000-0002-0026-9216", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e9d969adc0849ab83d0080430bb6758.json"}}, {"family": "Pirastu", "given": "Nicola", "initials": "N", "orcid": "0000-0002-5363-3886", "researcher": {"href": "https://publications.scilifelab.se/researcher/badf4678d37546ce993bccb3880d4f12.json"}}, {"family": "Gandin", "given": "Ilaria", "initials": "I", "orcid": "0000-0003-3196-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee19a08d128d40cf8bffcff35e37481d.json"}}, {"family": "Mattsson", "given": "Hannele", "initials": "H"}, {"family": "Barnes", "given": "Catriona L K", "initials": "CLK"}, {"family": "Lin", "given": "Kuang", "initials": "K"}, {"family": "Zhao", "given": "Jing Hua", "initials": "JH"}, {"family": "Deelen", "given": "Patrick", "initials": "P", "orcid": "0000-0002-5654-3966", "researcher": {"href": "https://publications.scilifelab.se/researcher/29b4f65a7b6e454d92315f99841f0e70.json"}}, {"family": "Rohde", "given": "Rebecca", "initials": "R"}, {"family": "Schurmann", "given": "Claudia", "initials": "C", "orcid": "0000-0003-4158-9192", "researcher": {"href": "https://publications.scilifelab.se/researcher/357aae1711d34a0e993b10c93c73cfb4.json"}}, {"family": "Guo", "given": "Xiuqing", "initials": "X"}, {"family": "Giulianini", "given": "Franco", "initials": "F"}, {"family": "Zhang", "given": "Weihua", "initials": "W"}, {"family": "Medina-Gomez", "given": "Carolina", "initials": "C", "orcid": "0000-0001-7999-5538", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1f97914d1c34f1f8190738c2d2e27b0.json"}}, {"family": "Karlsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-8949-2587", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df14bf33f3342408d624caa70d45b7c.json"}}, {"family": "Bao", "given": "Yanchun", "initials": "Y", "orcid": "0000-0002-6102-5098", "researcher": {"href": "https://publications.scilifelab.se/researcher/edd80af47df24a508164d6b550093563.json"}}, {"family": "Bartz", "given": "Traci M", "initials": "TM"}, {"family": "Baumbach", "given": "Clemens", "initials": "C"}, {"family": "Biino", "given": "Ginevra", "initials": "G", "orcid": "0000-0002-9936-946X", "researcher": {"href": "https://publications.scilifelab.se/researcher/791ca64b8e7c4930a8727ea9a52a5c15.json"}}, {"family": "Bixley", "given": "Matthew J", "initials": "MJ"}, {"family": "Brumat", "given": "Marco", "initials": "M", "orcid": "0000-0003-3268-039X", "researcher": {"href": "https://publications.scilifelab.se/researcher/422e5540e38047cfaa64708b0b118760.json"}}, {"family": "Chai", "given": "Jin-Fang", "initials": "JF", "orcid": "0000-0003-3770-1137", "researcher": {"href": "https://publications.scilifelab.se/researcher/7cac060e59cd405b94a588203b5955ca.json"}}, {"family": "Corre", "given": "Tanguy", "initials": "T"}, {"family": "Cousminer", "given": "Diana L", "initials": "DL"}, {"family": "Dekker", "given": "Annelot M", "initials": "AM"}, {"family": "Eccles", "given": "David A", "initials": "DA", "orcid": "0000-0003-4634-4995", "researcher": {"href": "https://publications.scilifelab.se/researcher/94670fee34be4f47ab7cf5c46a054fa4.json"}}, {"family": "van Eijk", "given": "Kristel R", "initials": "KR"}, {"family": "Fuchsberger", "given": "Christian", "initials": "C"}, {"family": "Gao", "given": "He", "initials": "H"}, {"family": "Germain", "given": "Marine", "initials": "M"}, {"family": "Gordon", "given": "Scott D", "initials": "SD", "orcid": "0000-0001-7623-328X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8815739662214e75b60f71f0b1ca58a6.json"}}, {"family": "de Haan", "given": "Hugoline G", "initials": "HG"}, {"family": "Harris", "given": "Sarah E", "initials": "SE", "orcid": "0000-0002-4941-5106", "researcher": {"href": "https://publications.scilifelab.se/researcher/1bbd06383e594035ab80af3bcdb29f91.json"}}, {"family": "Hofer", "given": "Edith", "initials": "E"}, {"family": "Huerta-Chagoya", "given": "Alicia", "initials": "A"}, {"family": "Igartua", "given": "Catherine", "initials": "C"}, {"family": "Jansen", "given": "Iris E", "initials": "IE"}, {"family": "Jia", "given": "Yucheng", "initials": "Y"}, {"family": "Kacprowski", "given": "Tim", "initials": "T", "orcid": "0000-0002-5393-2413", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5e640df1f184777a3066805d02a67c7.json"}}, {"family": "Karlsson", "given": "Torgny", "initials": "T", "orcid": "0000-0001-8095-6149", "researcher": {"href": "https://publications.scilifelab.se/researcher/691d6823b8e04c5abf1613513da32b08.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "Li", "given": "Shengchao Alfred", "initials": "SA"}, {"family": "Li-Gao", "given": "Ruifang", "initials": "R"}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications.scilifelab.se/researcher/194be8a851164e2ea4d004dd2febc9be.json"}}, {"family": "Matsuda", "given": "Koichi", "initials": "K", "orcid": "0000-0001-7292-2686", "researcher": {"href": "https://publications.scilifelab.se/researcher/016c48eb6c8341b7b593c4b1c9e39266.json"}}, {"family": "Meidtner", "given": "Karina", "initials": "K"}, {"family": "Meng", "given": "Weihua", "initials": "W", "orcid": "0000-0001-5388-8494", "researcher": {"href": "https://publications.scilifelab.se/researcher/cdb05cc4a7554f4d8fdc57ec60b542d2.json"}}, {"family": "Montasser", "given": "May E", "initials": "ME"}, {"family": "van der Most", "given": "Peter J", "initials": "PJ", "orcid": "0000-0001-8450-3518", "researcher": {"href": "https://publications.scilifelab.se/researcher/17cd11842111490ba5460f3093a366f3.json"}}, {"family": "Munz", "given": "Matthias", "initials": "M", "orcid": "0000-0002-4728-3357", "researcher": {"href": 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"initials": "BR"}, {"family": "Shriner", "given": "Daniel", "initials": "D"}, {"family": "Skotte", "given": "Line", "initials": "L", "orcid": "0000-0002-7398-1271", "researcher": {"href": "https://publications.scilifelab.se/researcher/8078f2481d644ec8a53c28570e9af119.json"}}, {"family": "Smart", "given": "Melissa C", "initials": "MC"}, {"family": "Smith", "given": "Albert Vernon", "initials": "AV"}, {"family": "van der Spek", "given": "Ashley", "initials": "A", "orcid": "0000-0001-7136-0159", "researcher": {"href": "https://publications.scilifelab.se/researcher/85d1ebe3cc5d4ff89d89a4dbead121de.json"}}, {"family": "Spracklen", "given": "Cassandra N", "initials": "CN", "orcid": "0000-0003-3590-7182", "researcher": {"href": "https://publications.scilifelab.se/researcher/132c3af299ef430294d5d2091f135e90.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": 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"given": "Guanjie", "initials": "G"}, {"family": "Chen", "given": "Yii-Der I", "initials": "YI"}, {"family": "Chen", "given": "Zhengming", "initials": "Z", "orcid": "0000-0001-6423-105X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bf7c7a02e2c4259b06821d341a7efdf.json"}}, {"family": "Chiu", "given": "Yen-Feng", "initials": "YF", "orcid": "0000-0002-3352-4500", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c9c21037563430db3db5901f5f22cb5.json"}}, {"family": "Cocca", "given": "Massimiliano", "initials": "M", "orcid": "0000-0002-1127-7596", "researcher": {"href": "https://publications.scilifelab.se/researcher/86431d25a54645e3988674b5e0ef6a59.json"}}, {"family": "Collins", "given": "Francis S", "initials": "FS", "orcid": "0000-0002-1023-7410", "researcher": {"href": "https://publications.scilifelab.se/researcher/10628a7a84cb4c7dbd6c161a8723ccbb.json"}}, {"family": "Concas", "given": "Maria Pina", "initials": "MP"}, {"family": "Corley", 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{"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"}]}