Fine Mapping and Identification of BMI Loci in African Americans

Jian Gong; Fredrick Schumacher; Unhee Lim; Lucia A Hindorff; Jeff Haessler; Steven Buyske; Christopher S Carlson; Stephanie Rosse; Petra Bůžková; Myriam Fornage; Myron Gross; Nathan Pankratz; James S Pankow; Pamela J Schreiner; Richard Cooper; Georg Ehret; C. Charles Gu; Denise Houston; Marguerite R Irvin; Rebecca Jackson; Lew Kuller; Brian Henderson; Iona Cheng; Lynne Wilkens; Mark Leppert; Cora E Lewis; Rongling Li; Khanh-Dung H Nguyen; Robert Goodloe; Eric Farber-Eger; Jonathan Boston; Holli H Dilks; Marylyn D Ritchie; Jay Fowke; Loreall Pooler; Misa Graff; Lindsay Fernandez-Rhodes; Barbara Cochrane; Eric Boerwinkle; Charles Kooperberg; Tara C Matise; Loic Le Marchand; Dana C Crawford; Christopher A Haiman; Kari E North; Ulrike Peters

doi:10.1016/j.ajhg.2013.08.012

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Fine Mapping and Identification of BMI Loci in African Americans

Journal article

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Peer reviewed

Fine Mapping and Identification of BMI Loci in African Americans

Jian Gong, Fredrick Schumacher, Unhee Lim, Lucia A Hindorff, Jeff Haessler, Steven Buyske, Christopher S Carlson, Stephanie Rosse, Petra Bůžková, Myriam Fornage, …

American journal of human genetics, Vol.93(4), pp.661-671

10/03/2013

DOI: https://doi.org/10.1016/j.ajhg.2013.08.012

PMCID: PMC3791273

PMID: 24094743

Abstract

Genome-wide association studies (GWASs) primarily performed in European-ancestry (EA) populations have identified numerous loci associated with body mass index (BMI). However, it is still unclear whether these GWAS loci can be generalized to other ethnic groups, such as African Americans (AAs). Furthermore, the putative functional variant or variants in these loci mostly remain under investigation. The overall lower linkage disequilibrium in AA compared to EA populations provides the opportunity to narrow in or fine-map these BMI-related loci. Therefore, we used the Metabochip to densely genotype and evaluate 21 BMI GWAS loci identified in EA studies in 29,151 AAs from the Population Architecture using Genomics and Epidemiology (PAGE) study. Eight of the 21 loci (SEC16B, TMEM18, ETV5, GNPDA2, TFAP2B, BDNF, FTO, and MC4R) were found to be associated with BMI in AAs at 5.8 × 10−5. Within seven out of these eight loci, we found that, on average, a substantially smaller number of variants was correlated (r2 > 0.5) with the most significant SNP in AA than in EA populations (16 versus 55). Conditional analyses revealed GNPDA2 harboring a potential additional independent signal. Moreover, Metabochip-wide discovery analyses revealed two BMI-related loci, BRE (rs116612809, p = 3.6 × 10−8) and DHX34 (rs4802349, p = 1.2 × 10−7), which were significant when adjustment was made for the total number of SNPs tested across the chip. These results demonstrate that fine mapping in AAs is a powerful approach for both narrowing in on the underlying causal variants in known loci and discovering BMI-related loci.

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Title: Fine Mapping and Identification of BMI Loci in African Americans
Creators: Jian Gong - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Fredrick Schumacher - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Unhee Lim - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
Lucia A Hindorff - Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Jeff Haessler - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Steven Buyske - Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA
Christopher S Carlson - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Stephanie Rosse - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Petra Bůžková - Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
Myriam Fornage - The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Myron Gross - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
Nathan Pankratz - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
James S Pankow - Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
Pamela J Schreiner - Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
Richard Cooper - Preventive Medicine and Epidemiology, Loyola University, Chicago, IL 60153, USA
Georg Ehret - Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
C. Charles Gu - Department of Biostatistics, Washington University, St. Louis, MO 63110, USA
Denise Houston - Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Marguerite R Irvin - Department of Biostatistics, University of Alabama, Birmingham, AL 35294, USA
Rebecca Jackson - Department of Internal Medicine, Ohio State Medical Center, Columbus, OH 43210, USA
Lew Kuller - Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
Brian Henderson - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Iona Cheng - Cancer Prevention Institute of California, Fremont, CA 94538, USA
Lynne Wilkens - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
Mark Leppert - Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
Cora E Lewis - Department of Medicine, University of Alabama, Birmingham, AL 35294, USA
Rongling Li - Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Khanh-Dung H Nguyen - Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Robert Goodloe - Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA
Eric Farber-Eger - Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA
Jonathan Boston - Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA
Holli H Dilks - Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA
Marylyn D Ritchie - Pennsylvania State University, State College, PA 16801, USA
Jay Fowke - Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN 37203, USA
Loreall Pooler - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Misa Graff - Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Lindsay Fernandez-Rhodes - Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Barbara Cochrane - Baylor College of Medicine, Houston, TX 77030, USA
Eric Boerwinkle - The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Charles Kooperberg - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Tara C Matise - Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA
Loic Le Marchand - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
Dana C Crawford - Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA
Christopher A Haiman - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Kari E North - Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27514, USA
Ulrike Peters - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Publication Details: American journal of human genetics, Vol.93(4), pp.661-671
Date published: 10/03/2013
Publisher: Elsevier Inc
Academic Unit: Statistics (SAS); Genetics (SAS)
Language: English
Resource Type: Journal article
Identifiers: 991031665346004646