Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations

Zammy Fairhurst-Hunter; Kuang Lin; Iona Y. Millwood; Alfred Pozarickij; Tzu‐Ting Chen; Jason Torres; Jian-an Lun; Christiana Kartsonaki; Wei Gan; Anubha Mahajan; Huaidong Du; Rajani Sohoni; Yu Guo; Sam Sansome; Ling Yang; Canqing Yu; Yiping Chen; Jun Lv; Gibran Hemani; Masaru Koido; Yoichiro Kamatani; Cassandra Nichole Spracklen; Penny Gordon‐Larsen; Mine Koprulu; Xiangrui Meng; Karoline B. Kuchenbaecker; Segun Fatumo; Laxmi Bhatta; Ben Michael Brumpton; Jesús Alegre-Díaz

doi:10.1101/2022.07.05.22277254

Genetic & Genomic MedicinemedRxivJul 5, 2022

Preprint

Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations

Zammy Fairhurst-Hunter, Kuang Lin iD, Iona Y. Millwood iD, Alfred Pozarickij iD, Tzu‐Ting Chen iD, Jason Torres iD, Jian-an Lun, Christiana Kartsonaki iD, Wei Gan iD, Anubha Mahajan iD, Huaidong Du iD, Rajani Sohoni, Yu Guo iD, Sam Sansome iD, Ling Yang iD, Canqing Yu iD, Yiping Chen iD, Jun Lv iD, Gibran Hemani iD, Masaru Koido iD, Yoichiro Kamatani iD, Cassandra Nichole Spracklen iD, Penny Gordon‐Larsen iD, Mine Koprulu iD, Xiangrui Meng iD, , Robin G. Walters iD

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Abstract

Genome-wide association studies (GWAS) in predominately European-ancestry (EUR) populations have identified numerous genetic variants associated with adiposity-related traits. An emerging challenge is the limited transferability of genetic scores constructed based on GWAS results from one ancestry for trait prediction in other ancestries. We performed trans-ancestry meta-analysis (TAMA) for eight adiposity-related traits using genetic data from 96,124 East Asian (EAS) and 443,359 EUR individuals. We identified >1400 genomic regions significantly associated with one or more traits. Despite EAS comprising only [~]20% of the study population, genetic scores constructed from the trans-ancestry (TA) results accounted for between 30% and 79% more variation in the adiposity traits in EAS compared with scores derived from the EUR GWAS alone. Furthermore, TA scores also modestly improved variance explained in African/African American, Hispanic and South Asian populations. Our findings highlight the utility of TAMA for increasing variance explained by genetic scores across populations of different ancestries.