Pulse lineResearch With Heart Logo

Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study.

TitleGeneralization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study.
Publication TypeJournal Article
Year of Publication2018
AuthorsHodonsky 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
Secondary AuthorsAvery CL
JournalAm J Hematol
Date Published2018 Jun 15
ISSN1096-8652
Abstract

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

DOI10.1002/ajh.25161
Alternate JournalAm J Hematol
PubMed ID29905378
PubMed Central IDPMC6300146
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
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 / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01 WH042114 / WH / WHI NIH HHS / United States
N01 WH032105 / WH / WHI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
N01WH32102 / WH / WHI NIH HHS / United States
N01 WH042107 / WH / WHI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
R01 HG009974 / HG / NHGRI NIH HHS / United States
N01 WH032109 / WH / WHI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 WH042108-011 / WH / WHI NIH HHS / United States
N01 HC085082 / HC / NHLBI 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
N01 WH042115 / WH / WHI NIH HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01 WH042113 / WH / WHI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 WH042119 / WH / WHI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01 WH042116 / WH / WHI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 WH042117 / WH / WHI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
N01 WH032106 / WH / WHI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01 WH042112 / WH / WHI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01WH32101 / WH / WHI NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 WH042120 / WH / WHI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01 WH032108 / WH / WHI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01 WH032119 / WH / WHI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
N01 WH032113 / WH / WHI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States