{"doi":"10.1038/ng.2507","title":"Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion","abstract":null,"journal":"Nature Genetics","year":2013,"id":591572,"datarank":10.958945663517769,"base_score":5.69035945432406,"endowment":5.69035945432406,"self_citation_contribution":0.8535539181486091,"citation_network_contribution":10.10539174536916,"self_endowment_contribution":0.8535539181486091,"citer_contribution":10.10539174536916,"corpus_percentile":null,"corpus_rank":null,"citation_count":295,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1513547,"name":"Anne U Jackson","orcid":null,"position":1,"is_corresponding":false},{"id":1513548,"name":"Marie P Fogarty","orcid":null,"position":2,"is_corresponding":false},{"id":1513549,"name":"Martin L Buchkovich","orcid":null,"position":3,"is_corresponding":false},{"id":14709,"name":"Alena Stančáková","orcid":"0000-0002-1375-0252","position":4,"is_corresponding":false},{"id":1513550,"name":"Heather M Stringham","orcid":null,"position":5,"is_corresponding":false},{"id":240625,"name":"Xueling Sim","orcid":"0000-0002-1233-7642","position":6,"is_corresponding":false},{"id":595919,"name":"Lingyao Yang","orcid":"0000-0001-8049-1505","position":7,"is_corresponding":false},{"id":16065,"name":"Christian Fuchsberger","orcid":"0000-0002-5918-8947","position":8,"is_corresponding":false},{"id":285374,"name":"Henna Cederberg","orcid":"0000-0003-2901-9373","position":9,"is_corresponding":false},{"id":1513551,"name":"Peter S Chines","orcid":null,"position":10,"is_corresponding":false},{"id":1513552,"name":"Tanya M Teslovich","orcid":null,"position":11,"is_corresponding":false},{"id":1513553,"name":"Jane M Romm","orcid":null,"position":12,"is_corresponding":false},{"id":630016,"name":"Hua Ling","orcid":"0000-0003-4414-8413","position":13,"is_corresponding":false},{"id":4199,"name":"Ivy McMullen","orcid":null,"position":14,"is_corresponding":false},{"id":505899,"name":"Roxann Ingersoll","orcid":null,"position":15,"is_corresponding":false},{"id":1513554,"name":"Elizabeth W Pugh","orcid":null,"position":16,"is_corresponding":false},{"id":1513555,"name":"Kimberly F Doheny","orcid":null,"position":17,"is_corresponding":false},{"id":677769,"name":"Benjamin M Neale","orcid":null,"position":18,"is_corresponding":false},{"id":1339580,"name":"Mark J Daly","orcid":null,"position":19,"is_corresponding":false},{"id":21907,"name":"Johanna Kuusisto","orcid":"0000-0001-6550-3176","position":20,"is_corresponding":false},{"id":1513556,"name":"Laura J Scott","orcid":null,"position":21,"is_corresponding":false},{"id":24782,"name":"Hyun Min Kang","orcid":"0000-0002-3631-3979","position":22,"is_corresponding":false},{"id":139250,"name":"Francis S Collins","orcid":null,"position":23,"is_corresponding":false},{"id":1513557,"name":"Gonçalo R Abecasis","orcid":null,"position":24,"is_corresponding":false},{"id":1513558,"name":"Richard M Watanabe","orcid":null,"position":25,"is_corresponding":false},{"id":1035,"name":"Michael Boehnke","orcid":"0000-0002-6442-7754","position":26,"is_corresponding":false},{"id":277044,"name":"Markku Laakso","orcid":"0000-0002-3394-7749","position":27,"is_corresponding":false},{"id":1513559,"name":"Karen L Mohlke","orcid":null,"position":28,"is_corresponding":false},{"id":1513546,"name":"Jeroen R Huyghe","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion","abstract":"Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.","is_dataset_classified":null,"base_score":5.69035945432406,"endowment":5.69035945432406,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23263489","pmcid":"PMC3727235","openalex_id":"https://openalex.org/W2061604798","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK020572","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK062370","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"Z01 HG000024","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"1Z01 HG000024","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK043351","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK062370","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK072193","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R56 DK062370","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK093757","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK062370","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK072193","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK093757","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"T32 HG000040","title":null},{"funder_name":"European Commission","grant_id":"201681","title":"NOVEL PREP1-DEPENDENT TRANSCRIPTIONAL NETWORKS IN THE CONTROL OF INSULIN SENSITIVITY"},{"funder_name":"National Institutes of Health","grant_id":"3R01DK093757-05S1","title":"Genetic epidemiology of rare and regulatory variants for metabolic traits"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK072193-16","title":"Targeted Genetic Analysis of T2D and Quantitative Traits"},{"funder_name":"Research Council of Finland","grant_id":"124243","title":"Identification of new genes for type 2 diabetes"}],"total_grants":17,"fwci":19.2864,"citation_percentile":0.99581424,"influential_citations":0,"citation_trend":[{"year":2013,"count":19},{"year":2014,"count":40},{"year":2015,"count":44},{"year":2016,"count":38},{"year":2017,"count":26},{"year":2018,"count":15},{"year":2019,"count":22},{"year":2020,"count":38},{"year":2021,"count":14},{"year":2022,"count":14},{"year":2023,"count":6},{"year":2024,"count":11},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"green","license":"Springer TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3727235","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3727235","host_type":"repository"},{"url":"http://www.nature.com/articles/ng.2507.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/ng.2507","host_type":"publisher"},{"url":"https://doi.org/10.1038/ng.2507","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23263489","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3727235","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc3727235?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.17615/63sx-0c91","host_type":""},{"url":"https://dx.doi.org/10.1038/ng.2507","host_type":""}],"fields_of_study":["Genetic Associations and Epidemiology","Pancreatic function and diabetes","Genetic Mapping and Diversity in Plants and Animals","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Insulin Secretion","Cytoskeletal Proteins","Fasting","Finland","Gene Frequency","Genetics, Population","Genotype","Humans","Mixed Function Oxygenases","Insulin","Male","Proinsulin","Genetic Variation","Amidine-Lyases","Guanine Nucleotide Exchange Factors","Tumor Suppressor Proteins","Intracellular Signaling Peptides and Proteins","Adaptor Proteins, Signal Transducing","Death Domain Receptor Signaling Adaptor Proteins","Molecular Sequence Annotation","Exome"],"keywords":["Biology","Genome-wide association study","Exome","Minor allele frequency","Genetics","Exome sequencing","Proinsulin","Single-nucleotide polymorphism","Allele frequency","Genotyping","Genetic association","Nonsynonymous substitution","Genetic architecture","Glucose homeostasis","Allele","Insulin","Gene","Genotype","Endocrinology","Phenotype","Genome","Insulin resistance","Male","Death Domain Receptor Signaling Adaptor Proteins","Intracellular Signaling Peptides and Proteins","Genetic Variation","Molecular Sequence Annotation","Fasting","Mixed Function Oxygenases","Cytoskeletal Proteins","Genetics, Population","Gene Frequency","Amidine-Lyases","Insulin Secretion","Guanine Nucleotide Exchange Factors","Humans","Finland","Adaptor Proteins, Signal Transducing"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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