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Int J Obes (Lond). 2018 Mar;42(3):384-390. doi: 10.1038/ijo.2017.304. Epub 2017 Dec 21.

Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.

Author information

1
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
2
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
3
Cancer Research Center, University of Hawaii, Honolulu, HI, USA.
4
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
7
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
8
Health Science Center, University of Texas, Austin, TX, USA.
9
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
10
Department of Biostatistics, University of Washington, Seattle, WA, USA.
11
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
12
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
13
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.
14
Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
15
Sarah Cannon Research Institute, Nashville, TN, USA.
16
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
17
Division of Cardiology, Geneva University Hospital, Geneva, Switzerland.
18
Department of Biostatistics, Washington University, St Louis, MO, USA.
19
Department of Medicine, University of Alabama, Birmingham, AL, USA.
20
Preventive Medicine and Epidemiology, Loyola University, Chicago, IL, USA.
21
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
22
Department of Epidemiology, University of Alabama, Birmingham, AL, USA.
23
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
24
Cancer Prevention Institute of California, Fremont, CA, USA.
25
Department of Internal Medicine, Ohio State Medical Center, Columbus, OH, USA.
26
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
27
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
28
Department of Genetics, Rutgers University, Piscataway, NJ, USA.
29
Department of Statistics and Biostatistics, Rutgers University, Piscataway, NJ, USA.
30
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
31
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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 (P<2.5 × 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.

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