Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

SUMMARY Most loci identified by GWAS have been found in populations of European ancestry (EA). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EA individuals, we identified 5,552 trait-variant associations at P<5×10−9, including 71 novel loci not found in EA populations. We also identified novel ancestry-specific variants not found in EA, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EA-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations, and compared genetic architecture and the impact of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

William J. Astle | Andrew D. Johnson | P. Elliott | J. Danesh | A. Reiner | T. Lehtimäki | T. Hansen | O. Pedersen | N. Grarup | Hua Tang | M. Kanai | Y. Kamatani | Y. Okada | W. Ouwehand | N. Watkins | H. Völzke | P. Wilson | A. Zonderman | M. Evans | K. Matsuda | O. Raitakari | Yongmei Liu | B. Psaty | C. Lareau | T. Esko | S. Karthikeyan | Michael H. Preuss | K. Mohlke | Yun Li | G. Lettre | J. Rotter | J. Brody | J. Tardif | N. Soranzo | U. Völker | N. Mononen | E. Bottinger | S. Rich | J. Howson | M. Kähönen | T. Bartz | A. Correa | Jingzhong Ding | E. Evangelou | M. Ghanbari | T. Kacprowski | Y. Ben-Shlomo | D. Heel | K. Hunt | J. Bork-Jensen | R. Loos | L. Lyytikäinen | M. Guo | E. Angelantonio | A. Butterworth | P. Auer | A. Linneberg | M. Nauck | M. Lerch | Bingshan Li | Erik L. Bao | Ming-Huei Chen | K. S. Lo | G. Nadkarni | J. Haessler | L. Broer | L. Lange | K. Nikus | P. Surendran | R. Trembath | C. Chiang | Wei Huang | A. Manichaikul | N. Dimou | T. Jiang | D. Roberts | N. Pankratz | Kelly Cho | E. Jorgenson | S. Sakaue | M. Akiyama | A. Greinacher | J. Huffman | H. Choquet | Y. Murakami | A. Moscati | X. Zhong | L. Raffield | P. Schubert | Regina Manansala | Huijun Qian | V. Sankaran | Q. Huang | H. Martin | J. Floyd | D. Vuckovic | A. Beswick | M. Beaudoin | F. V. Rooij | C. Spracklen | Jonathan D. Rosen | Michael H Preuss | P. Akbari | A. Mousas | K. Chitrala | F. Koskeridis | B. Rodriguez | Véronique Laplante | Minhui Chen | J. Gauchat | B. Trivedi | P. Elliott | Yun Li | S. Rich | Wei Huang | Peter W F Wilson | O. Raitakari | A. Johnson | V. Laplante | Frank J.A. van Rooij | Hua Tang

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