Genome-wide linkage and regional association study of obesity-related phenotypes: the GenSalt study

Obesity (Silver Spring). 2014 Feb;22(2):545-56. doi: 10.1002/oby.20469. Epub 2013 Jul 2.

Abstract

Objective: To identify chromosomal regions harboring quantitative trait loci for waist circumference (WC) and body mass index (BMI).

Design and methods: A genome-wide linkage scan and regional association study WC and BMI among 633 Chinese families was conducted.

Results: A significant linkage signal for WC was observed at 22q13.31-22q13.33 in the overall analysis (LOD = 3.13). Follow-up association study of 22q13.31-13.33 revealed an association between the TBC1D22A gene marker rs16996195 and WC (false discovery rate [FDR]-Q < 0.05). In gender-stratified analysis, suggestive linkage signals were attained for WC at 2p24.3-2q12.2 and 22q13.33 among females (LOD = 2.54 and 2.15, respectively). Among males, 6q12-6q13 was suggestively linked to BMI (LOD = 2.03). Single marker association analyses at these regions identified male-specific relationships of six single nucleotide polymorphisms (SNPs) at 2p24.3-2q12.2 (rs100955, rs13020676, rs13014034, rs12990515, rs17024325, and rs2192712) and five SNPs at 6q12-6q13 (rs7747318, rs7767301, rs12197115, rs12203049, and rs9454847) with the obesity-related phenotypes (all FDR-Q < 0.05). At chromosome 6q12-6q13, markers rs7755450 and rs11758293 predicted BMI in females (both FDR-Q < 0.05).

Conclusions: Genomic regions on chromosomes 2, 6, and 22 which may harbor important obesity-susceptibility loci were described. Follow-up study of these regions revealed several novel variants associated with obesity related traits. Future work to confirm these promising findings is warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Asian People
  • Body Mass Index
  • China
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 22*
  • Chromosomes, Human, Pair 6
  • Diet, Sodium-Restricted
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism
  • Genetic Association Studies
  • Genetic Linkage*
  • Genome-Wide Association Study
  • Humans
  • Hypertension / diet therapy
  • Hypertension / etiology*
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Polymorphism, Single Nucleotide*
  • Potassium, Dietary / therapeutic use
  • Quantitative Trait Loci*
  • Sex Characteristics
  • Waist Circumference

Substances

  • GTPase-Activating Proteins
  • Potassium, Dietary
  • TBC122B protein, human