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Trans-ethnic meta-analysis of white blood cell phenotypes.
Wednesday,2015-03-04 12:51 America/Los_Angeles — zdrager
| Title | Trans-ethnic meta-analysis of white blood cell phenotypes. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Keller, MF, Reiner, AP, Okada, Y, van Rooij, FJA, Johnson, AD, Chen, M-H, Smith, AV, Morris, AP, Tanaka, T, Ferrucci, L, Zonderman, AB, Lettre, G, Harris, T, Garcia, M, Bandinelli, S, Qayyum, R, Yanek, LR, Becker, DM, Becker, LC, Kooperberg, C, Keating, B, Reis, J, Tang, H, Boerwinkle, E, Kamatani, Y, Matsuda, K, Kamatani, N, Nakamura, Y, Kubo, M, Liu, S, Dehghan, A, Felix, JF, Hofman, A, Uitterlinden, AG, van Duijn, CM, Franco, OH, Longo, DL, Singleton, AB, Psaty, BM, Evans, MK, Cupples, AL, Rotter, JI, O'Donnell, CJ, Takahashi, A, Wilson, JG, Ganesh, SK, Nalls, MA |
| Corporate/Institutional Authors | CHARGE Hematology, COGENT, BioBank Japan Project (RIKEN) Working Groups |
| Journal | Hum Mol Genet |
| Volume | 23 |
| Issue | 25 |
| Pagination | 6944-60 |
| Date Published | 2014 Dec 20 |
| ISSN | 1460-2083 |
| Keywords | African Americans, Asian Continental Ancestry Group, Bayes Theorem, European Continental Ancestry Group, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Leukocyte Count, Leukocytes, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci |
| Abstract | <p>White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool. </p> |
| DOI | 10.1093/hmg/ddu401 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 25096241 |
| PubMed Central ID | PMC4245044 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States 32105-6 / / PHS HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States 098017 / / Wellcome Trust / United Kingdom N01-AG-821336 / AG / NIA NIH HHS / United States Z01-AG000513 / AG / NIA NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States N01-HC-55017 / HC / NHLBI NIH HHS / United States U01 HL107446 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States HHSN268201100005C / / PHS HHS / United States N01AG62101 / AG / NIA NIH HHS / United States HHSN268201100012C) / / PHS HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States 42107-26 / / PHS HHS / United States 32115 / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States 2009-149 / / PHS HHS / United States R01HL087698-01 / HL / NHLBI NIH HHS / United States N01-HC-45204 / HC / NHLBI NIH HHS / United States 263 MD 9164 13 / MD / NIMHD NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States R01 GM073059 / GM / NIGMS NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States M01-RR000052 / RR / NCRR NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States 32100-2 / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States 24152 / / PHS HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States RR03655 / RR / NCRR NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45134 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States 42129-32 / / PHS HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01 HL71862-06 / HL / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States 32118-32119 / / PHS HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States P30HL101290 / HL / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States 32108-9 / / PHS HHS / United States N000949304 / / PHS HHS / United States HHSN268201100007C / / PHS HHS / United States N01-HC-95171 / HC / NHLBI NIH HHS / United States N01-HC-95172 / HC / NHLBI NIH HHS / United States N01-AG-916413 / AG / NIA NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States AG000932-2 / AG / NIA NIH HHS / United States HHSN268201100011C / / PHS HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States N01-HC-95100 / HC / NHLBI NIH HHS / United States HHSN268200782096C / / PHS HHS / United States N01AG62106 / AG / NIA NIH HHS / United States 32122 / / PHS HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States HHSN268201100006C / / PHS HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States 44221 / / PHS HHS / United States WT064890 / / Wellcome Trust / United Kingdom 32111-13 / / PHS HHS / United States N01-HC-95170 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01NR08153 / NR / NINR NIH HHS / United States U01HL72518 / HL / NHLBI NIH HHS / United States |