title: Common body mass index-associated variants confer risk of extreme obesity.
abstract: To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at approximately 550,000 markers across the autosomal genome. We found convincing association to the previously described locus including the FTO gene. We also found evidence of association at a further six of 12 other loci previously reported to influence body mass index (BMI) in the general population and one of three associations to severe childhood and adult obesity and that cases have a higher proportion of risk-conferring alleles than controls. We found no evidence of homozygosity at any locus due to identity-by-descent associating with phenotype which would be indicative of rare, penetrant alleles, nor was there excess genome-wide homozygosity in cases relative to controls. Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition.
authors: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Chris
authors: C
authors: Cotsapas
authors: Elizabeth K
authors: EK
authors: Speliotes
authors: Ida J
authors: IJ
authors: Hatoum
authors: Danielle M
authors: DM
authors: Greenawalt
authors: Radu
authors: R
authors: Dobrin
authors: Pek Y
authors: PY
authors: Lum
authors: Christine
authors: C
authors: Suver
authors: Eugene
authors: E
authors: Chudin
authors: Daniel
authors: D
authors: Kemp
authors: Marc
authors: M
authors: Reitman
authors: Benjamin F
authors: BF
authors: Voight
authors: Benjamin M
authors: BM
authors: Neale
authors: Eric E
authors: EE
authors: Schadt
authors: Joel N
authors: JN
authors: Hirschhorn
authors: Lee M
authors: LM
authors: Kaplan
authors: Mark J
authors: MJ
authors: Daly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D005819:Genetic Markers