title: A genome-wide association study on obesity and obesity-related traits.
abstract: Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m(2)) and 540 control subjects (BMI<25 kg/m(2)), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5 × 10(-12)). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67 × 10(-9)), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS.
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
authors.forename: Clarence K
authors.initials: CK
authors.lastname: Zhang
authors.forename: Zuoheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: R Arlen
authors.initials: RA
authors.lastname: Price
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D055815:Young Adult