{"id":1150,"date":"2024-08-15T10:22:08","date_gmt":"2024-08-15T09:22:08","guid":{"rendered":"https:\/\/heliusstudy.nl\/?post_type=publicatie&#038;p=1150"},"modified":"2024-08-15T10:22:09","modified_gmt":"2024-08-15T09:22:09","slug":"trans-ethnic-meta-analysis-and-functional-annotation-illuminates-the-genetic-architecture-of-fasting-glucose-and-insulin","status":"publish","type":"publicatie","link":"https:\/\/heliusstudy.nl\/tr\/publicatie\/trans-ethnic-meta-analysis-and-functional-annotation-illuminates-the-genetic-architecture-of-fasting-glucose-and-insulin\/","title":{"rendered":"Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22\/54 EA-associated loci; 18\/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21\/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":true},"publications_year":[37],"thema":[42],"class_list":["post-1150","publicatie","type-publicatie","status-publish","hentry","publications_year-37","thema-cardiovascular-disease"],"acf":[],"_links":{"self":[{"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/publicatie\/1150","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/publicatie"}],"about":[{"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/types\/publicatie"}],"wp:attachment":[{"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/media?parent=1150"}],"wp:term":[{"taxonomy":"publications_year","embeddable":true,"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/publications_year?post=1150"},{"taxonomy":"thema","embeddable":true,"href":"https:\/\/heliusstudy.nl\/tr\/wp-json\/wp\/v2\/thema?post=1150"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}