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Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study.
Wednesday,2018-09-19 10:27 America/Los_Angeles — ecterry
| Title | Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Hodonsky, CJo, Schurmann, C, Schick, UM, Kocarnik, J, Tao, R, van Rooij, FJa, Wassel, C, Buyske, S, Fornage, M, Hindorff, LA, Floyd, JS, Ganesh, SK, Lin, D-Y, North, KE, Reiner, AP, Loos, RJf, Kooperberg, C, Avery, CL |
| Journal | Am J Hematol |
| Date Published | 2018 Jun 15 |
| ISSN | 1096-8652 |
| Abstract | <p>Red blood cell (RBC) traits provide insight into a wide range of physiological states and exhibit moderate to high heritability, making them excellent candidates for genetic studies to inform underlying biologic mechanisms. Previous RBC trait genome-wide association studies were performed primarily in European- or Asian-ancestry populations, missing opportunities to inform understanding of RBC genetic architecture in diverse populations and reduce intervals surrounding putative functional SNPs through fine-mapping. Here, we report the first fine-mapping of six correlated (Pearson's r range: |0.04 - 0.92|) RBC traits in up to 19,036 African Americans and 19,562 Hispanic/Latinos participants of the Population Architecture using Genomics and Epidemiology (PAGE) consortium. Trans-ethnic meta-analysis of race/ethnic- and study-specific estimates for approximately 11,000 SNPs flanking 13 previously identified association signals as well as 150,000 additional array-wide SNPs was performed using inverse-variance meta-analysis after adjusting for study and clinical covariates. Approximately half of previously reported index SNP-RBC trait associations generalized to the trans-ethnic study population (p<1.7x10 ); previously unreported independent association signals within the ABO region reinforce the potential for multiple functional variants affecting the same locus. Trans-ethnic fine-mapping did not reveal additional signals at the HFE locus independent of the known functional variants. Finally, we identified a potential novel association in the Hispanic/Latino study population at the HECTD4/RPL6 locus for RBC count (p=1.9x10 ). The identification of a previously unknown association, generalization of a large proportion of known association signals, and refinement of known association signals all exemplify the benefits of genetic studies in diverse populations. This article is protected by copyright. All rights reserved.</p> |
| DOI | 10.1002/ajh.25161 |
| Alternate Journal | Am. J. Hematol. |
| PubMed ID | 29905378 |
| Grant List | N01 WH032112 / WH / WHI NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States P01 HL060030 / HL / NHLBI NIH HHS / United States N01 WH32115 / WH / WHI NIH HHS / United States N01 HC085083 / HC / WHI NIH HHS / United States N01 WH042114 / WH / WHI NIH HHS / United States N01 WH032105 / WH / WHI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States N01 WH042107 / WH / WHI NIH HHS / United States N01 HC085086 / HC / WHI NIH HHS / United States N01 WH032109 / WH / WHI NIH HHS / United States N01 HC085082 / HC / WHI NIH HHS / United States N01 WH032100 / WH / WHI NIH HHS / United States N01 WH042121 / WH / WHI NIH HHS / United States N01 WH032111 / WH / WHI NIH HHS / United States N01 WH032122 / WH / WHI NIH HHS / United States N01 WH032118 / WH / WHI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01 WH042119 / WH / WHI NIH HHS / United States N01 WH042116 / WH / WHI NIH HHS / United States N01 HC055018 / HC / WHI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 WH042117 / WH / WHI NIH HHS / United States N01 HC055016 / HC / WHI NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States N01 HC085080 / HC / WHI NIH HHS / United States N01 WH032106 / WH / WHI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01 WH042112 / WH / WHI NIH HHS / United States N01 HC055019 / HC / WHI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01 WH032108 / WH / WHI NIH HHS / United States N01 WH032113 / WH / WHI NIH HHS / United States U01 HG004801 / HG / NHGRI NIH HHS / United States |
ePub date:
18/06