作者
Angli Xue,Yang Wu,Zhihong Zhu,Futao Zhang,Kathryn E. Kemper,Zhili Zheng,Loïc Yengo,Luke R. Lloyd‐Jones,Julia Sidorenko,Yeda Wu,Mawussé Agbessi,Habibul Ahsan,Isabel Alves,Anand Kumar Andiappan,Philip Awadalla,Alexis Battle,Frank Beutner,Marc Jan Bonder,Dorret I. Boomsma,Mark Christiansen,Annique Claringbould,Patrick Deelen,Tõnu Esko,Marie-Julie Favé,Lude Franke,Timothy M. Frayling,Sina A. Gharib,Gregory Gibson,Gibran Hemani,Rick Jansen,Mika Kähönen,Anette Kalnapenkis,Silva Kasela,Johannes Kettunen,Yungil Kim,Holger Kirsten,Péter Kovács,Knut Krohn,Jaanika Kronberg-Guzman,Viktorija Kukushkina,Zoltán Kutalik,Bernett Lee,Terho Lehtimäki,Markus Loeffler,Urko M. Marigorta,Andres Metspalu,Lili Milani,Martina Müller‐Nurasyid,Matthias Nauck,Michel G. Nivard,Brenda W.J.H. Penninx,Markus Perola,Natalia Pervjakova,Brandon L. Pierce,Joseph E. Powell,Holger Prokisch,Bruce M. Psaty,Olli T. Raitakari,Susan M. Ring,Samuli Ripatti,Olaf Rötzschke,Sina Rüeger,Ashis Saha,Markus Scholz,Katharina Schramm,Ilkka Seppälä,Michael Stümvoll,Iván Cárcamo-Orive,Alexander Teumer,Joachim Thiery,Tong Lin,Anke Tönjes,Jenny van Dongen,Joyce B. J. van Meurs,Joost Verlouw,Uwe Völker,Urmo Võsa,Hanieh Yaghootkar,Biao Zeng,Allan F. McRae,Peter M. Visscher,Jian Zeng,Jian Yang
摘要
Abstract Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood ( n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation ( n = 1980) and epigenomic annotation data highlight 3 genes ( CAMK1D , TP53INP1 , and ATP5G1 ) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.