CHS Home | Welcome New Investigators | Directory | Contact Us

 

You are here

Home

Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci.

Thursday,2017-09-14 12:16 America/Los_Angeles — ecterry
TitleTrans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci.
Publication TypeJournal Article
Year of Publication2017
AuthorsFernandez-Rhodes, L, Gong, J, Haessler, J, Franceschini, N, Graff, M, Nishimura, KK, Wang, Y, Highland, HM, Yoneyama, S, Bush, WS, Goodloe, R, Ritchie, MD, Crawford, D, Gross, M, Fornage, M, Bůzková, P, Tao, R, Isasi, C, Avilés-Santa, L, Daviglus, M, Mackey, RH, Houston, D, C Gu, C, Ehret, G, Nguyen, K-DH, Lewis, CE, Leppert, M, Irvin, MR, Lim, U, Haiman, CA, Le Marchand, L, Schumacher, F, Wilkens, L, Lu, Y, Bottinger, EP, Loos, RJL, Sheu, WH-H, Guo, X, Lee, W-J, Hai, Y, Hung, Y-J, Absher, D, Wu, I-C, Taylor, KD, Lee, I-T, Liu, Y, Wang, T-D, Quertermous, T, Juang, J-MJ, Rotter, JI, Assimes, T, Hsiung, CA, Chen, Y-DI, Prentice, R, Kuller, LH, Manson, JAE, Kooperberg, C, Smokowski, P, Robinson, WR, Gordon-Larsen, P, Li, R, Hindorff, L, Buyske, S, Matise, TC, Peters, U, North, KE
JournalHum Genet
Volume136
Issue6
Pagination771-800
Date Published2017 Jun
ISSN1432-1203
KeywordsBody Mass Index, Ethnic Groups, Genetics, Population, Humans, Obesity
Abstract<p>Most body mass index (BMI) genetic loci have been identified in studies of primarily European ancestries. The effect of these loci in other racial/ethnic groups is less clear. Thus, we aimed to characterize the generalizability of 170 established BMI variants, or their proxies, to diverse US populations and trans-ethnically fine-map 36 BMI loci using a sample of >102,000 adults of African, Hispanic/Latino, Asian, European and American Indian/Alaskan Native descent from the Population Architecture using Genomics and Epidemiology Study. We performed linear regression of the natural log of BMI (18.5-70 kg/m(2)) on the additive single nucleotide polymorphisms (SNPs) at BMI loci on the MetaboChip (Illumina, Inc.), adjusting for age, sex, population stratification, study site, or relatedness. We then performed fixed-effect meta-analyses and a Bayesian trans-ethnic meta-analysis to empirically cluster by allele frequency differences. Finally, we approximated conditional and joint associations to test for the presence of secondary signals. We noted directional consistency with the previously reported risk alleles beyond what would have been expected by chance (binomial p < 0.05). Nearly, a quarter of the previously described BMI index SNPs and 29 of 36 densely-genotyped BMI loci on the MetaboChip replicated/generalized in trans-ethnic analyses. We observed multiple signals at nine loci, including the description of seven loci with novel multiple signals. This study supports the generalization of most common genetic loci to diverse ancestral populations and emphasizes the importance of dense multiethnic genomic data in refining the functional variation at genetic loci of interest and describing several loci with multiple underlying genetic variants.</p>
DOI10.1007/s00439-017-1787-6
Alternate JournalHum. Genet.
PubMed ID28391526
PubMed Central IDPMC5485655
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
UM1 CA164973 / CA / NCI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
U01 HG007416 / HG / NHGRI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R25 CA094880 / CA / NCI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R01 CA063464 / CA / NCI NIH HHS / United States
P01 CA033619 / CA / NCI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
UL1 TR001073 / TR / NCATS NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
U01 CA098758 / CA / NCI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HD057194 / HD / NICHD NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
U01 HG007397 / HG / NHGRI NIH HHS / United States
U01 CA164973 / CA / NCI NIH HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States
ePub date: 
17/06

© 2001 - 2020 CHS Coordinating Center University of Washington, Seattle, WA

Privacy | Terms