title: Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study.
abstract: BACKGROUND
  Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans-a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population.
  
  
  OBJECTIVE
  To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR, MC4R, NPY2R and POMC genes.
  
  
  METHODS
  A genetic association study.
  
  
  METHODS
  990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans).
  
  
  METHODS
  The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population for FTO, LEP and NPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life.
  
  
  RESULTS
  Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI.
  
  
  CONCLUSIONS
  The study highlighted SNPs in FTO and MC4R as potential genetic markers of obesity risk in South Africans. The association with two SNPs in the 3' untranslated region of the LEP gene is novel.
authors.affiliation: Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Zané
authors.initials: Z
authors.lastname: Lombard
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Crowther
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Punita
authors.initials: P
authors.lastname: Pitamber
authors.forename: Shane A
authors.initials: SA
authors.lastname: Norris
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay