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Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.

par Piron, Anthony ;Szymczak, Florian ;Folon, Lise ;Crouch, Daniel J M;Papadopoulou, Theodora ;Lytrivi, Maria ;Tong, Yue ;Alvelos, Maria Inês;Colli, Maikel Luis ;Yi, Xiaoyan ;Pekalski, Marcin ML;Hatzikotoulas, Konstantinos;Huerta-Chagoya, Alicia;Taylor, Henry J;Type 2 Diabetes Global Genomics Initiative, Matthieu;Defrance, John A ;Todd, Décio L;Eizirik, Josep Maria;Mercader, Miriam;Cnop,
Référence Cell Genomics, page (101004)
Publication Publié, 2025-09

Article révisé par les pairs

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Résumé :

Over 1,000 genetic variants have been associated with diabetes by genome-wide association studies (GWASs), but for most, their functional impact is unknown; only 7% alter gene expression in pancreatic islets in expression quantitative trait locus (eQTL) studies. To fill this gap, we developed a co-localization pipeline, colocRedRibbon, that prefilters eQTLs by the direction of effect on gene expression and shortlists overlapping eQTL and GWAS variants prior to co-localization. Applying colocRedRibbon to recent diabetes and glycemic trait GWASs, we identified 292 co-localizing gene regions, including 24 co-localizations for type 1 diabetes and 268 for type 2 diabetes and glycemic traits, representing a 4-fold increase. A low-frequency type 2 diabetes protective variant increases islet MYO5C expression, and a type 1 diabetes protective variant increases FUT2 expression. These novel co-localizations advance the understanding of diabetes genetics and its impact on human islet biology. colocRedRibbon has broad applicability to co-localize GWASs and various QTLs.