Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations
Fairhurst-Hunter, Z.; Lin, K.; Millwood, I. Y.; Pozarickij, A.; Chen, T.-T.; Torres, J. M.; Luan, J.-a.; Kartsonaki, C.; Gan, W.; Mahajan, A.; Du, H.; Sohoni, R.; Guo, Y.; Sansome, S.; Yang, L.; Yu, C.; Chen, Y.; Lv, J.; Hemani, G.; Koido, M.; Kamatani, Y.; Spracklen, C. N.; Gordon-Larsen, P.; Koprulu, M.; Meng, X.; Kuchenbaecker, K.; Fatumo, S.; Bhatta, L.; Brumpton, B.; Alegre-Diaz, J.; Kuri-Morales, P.; Tapia-Conyer, R.; Graham, S. E.; Willer, C. J.; Neville, M. J.; Karpe, F.; Graff, M.; North, K. E.; Loos, R. J. F.; Haiman, C. A.; Peters, U.; Buskye, S.; Gignoux, C. R.; Wojcik, G.; Lin, Y.
Show 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.
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