Authors: | Gong, J; Nishimura, K. K.; Fernandez-Rhodes, L.; Haessler, J.; Bien, S.; Graff, M; Lim, U; Lu, Y; Gross, M.; Fornage, M; Yoneyama, S.; Isasi, C. R.; Buzkova, P.; Daviglus, M; Lin, D. Y.; Tao, R.; Goodloe, R.; Bush, W. S.; Farber-Eger, E.; Boston, J.; Dilks, H. H.; Ehret, G; Gu, C. C.; Lewis, C. E.; Nguyen, K. H.; Cooper, R; Leppert, M.; Irvin, M. R.; Bottinger, E. P.; Wilkens, L. R.; Haiman, C. A.; Park, L.; Monroe, K. R.; Cheng, I.; Stram, D. O.; Carlson, C. S.; Jackson, R.; Kuller, L; Houston, D.; Kooperberg, C; Buyske, S; Hindorff, L. A.; Crawford, D. C.; Loos, R. J. F.; Le Marchand, L; Matise, T. C.; North, K. E.; Peters, U |
Article Title: | Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI |
Abstract: | OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models. RESULTS: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (Plt;2.5 x 10(-)(7)). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue. CONCLUSION: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations. |
Journal Title: | International journal of obesity (2005) |
Volume: | 42 |
Issue: | 3 |
ISSN: | 1476-5497; 0307-0565 |
Publisher: | Unknown |
Journal Place: | England |
Date Published: | 2018 |
Start Page: | 384 |
End Page: | 390 |
Language: | eng |
DOI/URL: | |
Notes: | LR: 20180425; GR: HHSN268201100012C/HL/NHLBI NIH HHS/United States; GR: U01 HG007417/HG/NHGRI NIH HHS/United States; GR: N01WH42129/WH/WHI NIH HHS/United States; GR: UL1 RR033176/RR/NCRR NIH HHS/United States; GR: N01WH32111/WH/WHI NIH HHS/United States; GR: N01WH32100/WH/WHI NIH HHS/United States; GR: N01WH42125/WH/WHI NIH HHS/United States; GR: HHSN268201100001I/HL/NHLBI NIH HHS/United States; GR: HHSN268201100009I/HL/NHLBI NIH HHS/United States; GR: N01WH42124/WH/WHI NIH HHS/United States; GR: UL1 TR000445/TR/NCATS NIH HHS/United States; GR: HHSN268201300026C/HL/NHLBI NIH HHS/United States; GR: N01WH32109/WH/WHI NIH HHS/United States; GR: U01 HG007419/HG/NHGRI NIH HHS/United States; GR: N01WH32122/WH/WHI NIH HHS/United States; GR: U01 HL041642/HL/NHLBI NIH HHS/United States; GR: UM1 CA164973/CA/NCI NIH HHS/United States; GR: N01WH42120/WH/WHI NIH HHS/United States; GR: N01WH44221/WH/WHI NIH HHS/United States; GR: U01 HL041654/HL/NHLBI NIH HHS/United States; GR: N01WH42132/WH/WHI NIH HHS/United States; 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GR: R01 HL055673/HL/NHLBI NIH HHS/United States; GR: U01 HL065520/HL/NHLBI NIH HHS/United States; GR: N01WH42108/WH/WHI NIH HHS/United States; GR: HHSN268201100004C/WH/WHI NIH HHS/United States; GR: N01 HC065235/HC/WHI NIH HHS/United States; GR: N01HC48048/HL/NHLBI NIH HHS/United States; GR: N01WH42122/WH/WHI NIH HHS/United States; GR: N01HC85081/HL/NHLBI NIH HHS/United States; GR: N01WH42110/WH/WHI NIH HHS/United States; GR: U01 HG004801/HG/NHGRI NIH HHS/United States; GR: N01WH32112/WH/WHI NIH HHS/United States; JID: 101256108; NIHMS922308; PMCR: 2018/06/21 00:00; 2016/11/30 00:00 [received]; 2017/11/03 00:00 [revised]; 2017/11/21 00:00 [accepted]; 2018/06/21 00:00 [pmc-release]; 2018/01/31 06:00 [pubmed]; 2018/01/31 06:00 [medline]; 2018/01/31 06:00 [entrez]; ppublish |