Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation Academic Article uri icon

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abstract

  • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

authors

  • Mahajan, Anubha
  • Spracklen, Cassandra N
  • Zhang, Weihua
  • Ng, Maggie CY
  • Petty, Lauren E
  • Kitajima, Hidetoshi
  • Yu, Grace Z
  • Rüeger, Sina
  • Speidel, Leo
  • Kim, Young Jin
  • Horikoshi, Momoko
  • Mercader, Josep M
  • Taliun, Daniel
  • Moon, Sanghoon
  • Kwak, Soo-Heon
  • Robertson, Neil R
  • Rayner, Nigel W
  • Loh, Marie
  • Kim, Bong-Jo
  • Chiou, Joshua
  • Miguel-Escalada, Irene
  • della Briotta Parolo, Pietro
  • Lin, Kuang
  • Bragg, Fiona
  • Preuss, Michael H
  • Takeuchi, Fumihiko
  • Nano, Jana
  • Guo, Xiuqing
  • Lamri, Amel
  • Nakatochi, Masahiro
  • Scott, Robert A
  • Lee, Jung-Jin
  • Huerta-Chagoya, Alicia
  • Graff, Mariaelisa
  • Chai, Jin-Fang
  • Parra, Esteban J
  • Yao, Jie
  • Bielak, Lawrence F
  • Tabara, Yasuharu
  • Hai, Yang
  • Steinthorsdottir, Valgerdur
  • Cook, James P
  • Kals, Mart
  • Grarup, Niels
  • Schmidt, Ellen M
  • Pan, Ian
  • Sofer, Tamar
  • Wuttke, Matthias
  • Sarnowski, Chloe
  • Gieger, Christian
  • Nousome, Darryl
  • Trompet, Stella
  • Long, Jirong
  • Sun, Meng
  • Tong, Lin
  • Chen, Wei-Min
  • Ahmad, Meraj
  • Noordam, Raymond
  • Lim, Victor JY
  • Tam, Claudia HT
  • Joo, Yoonjung Yoonie
  • Chen, Chien-Hsiun
  • Raffield, Laura M
  • Lecoeur, Cécile
  • Prins, Bram Peter
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  • Ikram, Mohammad Arfan
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  • Yengo, Loïc
  • Yoon, Kyungheon
  • Yu, Canqing
  • Yuan, Jian-Min
  • Yusuf, Salim
  • Zhang, Liang
  • Zheng, Wei
  • Rüeger, Sina
  • della Briotta Parolo, Pietro
  • Joo, Yoonjung Yoonie
  • Hayes, M Geoffrey
  • Raffel, Leslie J
  • Igase, Michiya
  • Ipp, Eli
  • Redline, Susan
  • Cho, Yoon Shin
  • Lind, Lars
  • Province, Michael A
  • Hanis, Craig L
  • Peyser, Patricia A
  • Ingelsson, Erik
  • Zonderman, Alan B
  • Psaty, Bruce M
  • Wang, Ya-Xing
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  • Becker, Diane M
  • Matsuda, Fumihiko
  • Liu, Yongmei
  • Zeggini, Eleftheria
  • Yokota, Mitsuhiro
  • Rich, Stephen S
  • Kooperberg, Charles
  • Pankow, James S
  • Engert, James C
  • Chen, Yii-Der Ida
  • Froguel, Philippe
  • Wilson, James G
  • Sheu, Wayne HH
  • Kardia, Sharon LR
  • Wu, Jer-Yuarn
  • Hayes, M Geoffrey
  • Ma, Ronald CW
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  • Groop, Leif
  • Mook-Kanamori, Dennis O
  • Chandak, Giriraj R
  • Collins, Francis S
  • Bharadwaj, Dwaipayan
  • Pare, Guillaume
  • Sale, Michèle M
  • Ahsan, Habibul
  • Motala, Ayesha A
  • Shu, Xiao-Ou
  • Park, Kyong-Soo
  • Jukema, J Wouter
  • Cruz, Miguel
  • McKean-Cowdin, Roberta
  • Grallert, Harald
  • Cheng, Ching-Yu
  • Bottinger, Erwin P
  • Dehghan, Abbas
  • Tai, E-Shyong
  • Dupuis, Josée
  • Kato, Norihiro
  • Laakso, Markku
  • Köttgen, Anna
  • Koh, Woon-Puay
  • Palmer, Colin NA
  • Liu, Simin
  • Abecasis, Goncalo
  • Kooner, Jaspal S
  • Loos, Ruth JF
  • North, Kari E
  • Haiman, Christopher A
  • Florez, Jose C
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  • Mägi, Reedik
  • Langenberg, Claudia
  • Wareham, Nicholas J
  • Maeda, Shiro
  • Kadowaki, Takashi
  • Lee, Juyoung
  • Millwood, Iona Y
  • Walters, Robin G
  • Stefansson, Kari
  • Myers, Simon R
  • Ferrer, Jorge
  • Gaulton, Kyle J
  • Meigs, James B
  • Mohlke, Karen L
  • Gloyn, Anna L
  • Bowden, Donald W
  • Below, Jennifer E
  • Chambers, John C
  • Sim, Xueling
  • Boehnke, Michael
  • Rotter, Jerome I
  • McCarthy, Mark I
  • Morris, Andrew P

publication date

  • May 2022