Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.
- Xue, A.
- Wu, Y.
- Zhu, Z.
- Zhang, F.
- Kemper, K.E.
- Zheng, Z.
- Yengo, L.
- Lloyd-Jones, L.R.
- Sidorenko, J.
- eQTLGen Consortium
- Agbessi, M.
- Ahsan, H.
- Alves, I.
- Andiappan, A.K.
- Awadalla, P.
- Battle, A.
- Beutner, F.
- Bonder, M.J.
- Boomsma, D.
- Christiansen, M.W.
- Claringbould, A.
- Deelen, P.
- Esko, T.
- Favé, M.J.
- Franke, L.
- Frayling, T.
- Gharib, S.A.
- Gibson, G.
- Hemani, G.
- Jansen, R.
- Kähönen, M.
- Kalnapenkis, A.
- Kasela, S.
- Kettunen, J.
- Kim, Y.
- Kirsten, H.
- Kovacs, P.
- Krohn, K.
- Kronberg-Guzman, J.
- Kukushkina, V.
- Kutalik, Z.
- Lee, B.
- Lehtimäki, T.
- Loeffler, M.
- Marigorta, U.M.
- Metspalu, A.
- Milani, L.
- eQTLGen Consortium (Müller-Nurasyid, M.
- Nauck, M.
- Nivard, M.
- Penninx, B.
- Perola, M.
- Pervjakova, N.
- Pierce, B.F.
- Powell, J.
- Psaty, B.
- Raitakari, O.
- Ring, S.
- Ripatti, S.
- Rotzschke, O.
- Ruëger, S.
- Saha, A.
- Scholz, M.
- Seppälä, I.
- Stumvoll, M.
- Sullivan, P.F.
- Teumer, A.
- Thiery, J.
- Tong, L.
- Tönjes, A.
- van Dongen, J.
- van Meurs, J.B.
- Verlouw, J.
- Völker, U.
- Võsa, U.
- Yaghootkar, H.
- Zeng, B.
- McRae, A.F.
- Visscher, P.M.
- Zeng, J.
- Yang, J.
DOIAbstract
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 geneti...
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