02961nas a2200325   4500008004100000022001400041245012600055210006900181260001600250520195800266100002402224700002302248700002202271700002302293700001302316700002502329700002202354700001802376700002002394700002302414700002002437700002202457700001602479700001902495700002002514700001902534700002402553700002202577856003602599       2018                        eng d  a1096-865200aGeneralization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study.0 aGeneralization and fine mapping of red blood cell trait genetic   c2018 Jun 153 a<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>1 aHodonsky, Chani, Jo1 aSchurmann, Claudia1 aSchick, Ursula, M1 aKocarnik, Jonathan1 aTao, Ran1 avan Rooij, Frank, Ja1 aWassel, Christina1 aBuyske, Steve1 aFornage, Myriam1 aHindorff, Lucia, A1 aFloyd, James, S1 aGanesh, Santhi, K1 aLin, Dan-Yu1 aNorth, Kari, E1 aReiner, Alex, P1 aLoos, Ruth, Jf1 aKooperberg, Charles1 aAvery, Christy, L  uhttps://chs-nhlbi.org/node/7793