Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Anubha Mahajan; Cassandra Nichole Spracklen; Weihua Zhang; Maggie C.Y. Ng; Lauren E. Petty; Hidetoshi Kitajima; Grace Z. Yu; Sina Rüeger; Leo Speidel; Young Jin Kim; Momoko Horikoshi; Josep Maria Mercader; Daniel Taliun; Sanghoon Moon; Soo‐Heon Kwak; Neil R. Robertson; N. William Rayner; Marie Loh; Bong-Jo Kim; Joshua Chiou; Irene Miguel-Escalada; Pietro Della Briotta Parolo; Kuang Lin; Fiona Bragg; Michael H Preuss; Fumihiko Takeuchi; Jana Nano; Xiuqing Guo; Amel Lamri; Masahiro Nakatochi

doi:10.1038/s41588-022-01058-3

Genetic & Genomic MedicineDiscovery Research Portal (University of Dundee)Jan 1, 2022

Peer-reviewed journal article

Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Anubha Mahajan iD, Cassandra Nichole Spracklen iD, Weihua Zhang, Maggie C.Y. Ng iD, Lauren E. Petty iD, Hidetoshi Kitajima iD, Grace Z. Yu, Sina Rüeger iD, Leo Speidel iD, Young Jin Kim iD, Momoko Horikoshi iD, Josep Maria Mercader iD, Daniel Taliun iD, Sanghoon Moon iD, Soo‐Heon Kwak iD, Neil R. Robertson, N. William Rayner, Marie Loh iD, Bong-Jo Kim, Joshua Chiou iD, Irene Miguel-Escalada iD, Pietro Della Briotta Parolo, Kuang Lin, Fiona Bragg iD, Michael H Preuss iD, , Mary Cushman iD

Abstract

We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

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