{"entity": "publication", "iuid": "38ade6881a5c4c4aa4aeabe2fe7eb85d", "timestamp": "2026-07-22T22:58:12.861Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/38ade6881a5c4c4aa4aeabe2fe7eb85d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/38ade6881a5c4c4aa4aeabe2fe7eb85d"}}, "title": "Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation.", "authors": [{"family": "Strawbridge", "given": "Rona J", "initials": "RJ"}, {"family": "Silveira", "given": "Angela", "initials": "A"}, {"family": "Hoed", "given": "Marcel den", "initials": "MD"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Luan", "given": "Jian'an", "initials": "J"}, {"family": "Rybin", "given": "Denis", "initials": "D"}, {"family": "Dupuis", "given": "Jos\u00e9e", "initials": "J"}, {"family": "Li-Gao", "given": "Ruifang", "initials": "R"}, {"family": "Kavousi", "given": "Maryam", "initials": "M"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Haljas", "given": "Kadri", "initials": "K"}, {"family": "Lahti", "given": "Jari", "initials": "J"}, {"family": "G\u00e5din", "given": "Jesper R", "initials": "JR"}, {"family": "B\u00e4cklund", "given": "Alexandra", "initials": "A"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Gertow", "given": "Karl", "initials": "K"}, {"family": "Giral", "given": "Phillipe", "initials": "P"}, {"family": "Goel", "given": "Anuj", "initials": "A"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "Kurl", "given": "Sudhir", "initials": "S"}, {"family": "Langenberg", "given": "Claudia", "initials": "C"}, {"family": "Lannfelt", "given": "Lars L", "initials": "LL"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Lindgren", "given": "Cecilia C M", "initials": "CCM"}, {"family": "Mannarino", "given": "Elmo", "initials": "E"}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "de Mutsert", "given": "Ren\u00e9e", "initials": "R"}, {"family": "Rauramaa", "given": "Rainer", "initials": "R"}, {"family": "Saliba-Gustafsson", "given": "Peter", "initials": "P"}, {"family": "Sennblad", "given": "Bengt", "initials": "B"}, {"family": "Smit", "given": "Andries J", "initials": "AJ"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Zethelius", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Bj\u00f6rck", "given": "Hanna M", "initials": "HM"}, {"family": "Eriksson", "given": "Johan G", "initials": "JG"}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "Franco", "given": "Oscar H", "initials": "OH"}, {"family": "Watkins", "given": "Hugh", "initials": "H"}, {"family": "Jukema", "given": "J Wouter", "initials": "JW"}, {"family": "Florez", "given": "Jose C", "initials": "JC"}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Meigs", "given": "James B", "initials": "JB"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "IMPROVE study group", "given": "", "initials": ""}], "type": "journal article", "published": "2017-09-28", "journal": {"volume": "266", "issn": "1879-1484", "issue": null, "pages": "196-204", "title": "Atherosclerosis", "issn-l": "0021-9150"}, "abstract": "Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.\n\nWe studied the high CVD-risk IMPROVE cohort (n\u00a0=\u00a03345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n\u00a0=\u00a0904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.\n\nWe identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.\n\nWe identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.", "doi": "10.1016/j.atherosclerosis.2017.09.031", "pmid": "29040868", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9150(17)31317-5"}], "notes": [], "created": "2017-10-25T15:41:50.212Z", "modified": "2024-01-16T13:48:47.500Z"}