title: Genetic risk factors for BMI and obesity in an ethnically diverse population: results from the population architecture using genomics and epidemiology (PAGE) study.
abstract: OBJECTIVE
  Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups.
  
  
  METHODS
  As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI.
  
  
  RESULTS
  By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians.
  
  
  CONCLUSIONS
  Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.
authors.affiliation: Department of Biostatistics and Biomathematics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Fesinmeyer
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
authors.forename: Petra
authors.initials: P
authors.lastname: Bůžková
authors.forename: Kimberly
authors.initials: K
authors.lastname: Glenn
authors.forename: P Miguel
authors.initials: PM
authors.lastname: Quibrera
authors.forename: Lindsay
authors.initials: L
authors.lastname: Fernández-Rhodes
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Christina T L
authors.initials: CT
authors.lastname: Chen
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Steven
authors.initials: S
authors.lastname: Buyske
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D056186:Metagenomics / Q000379:methods*; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors