Genome-wide Linkage and Regional Association Study of Obesity-related Phenotypes: The GenSalt study

OBJECTIVE: To identify chromosomal regions harboring quantitative trait loci (QTL) for waist circumference (WC) and body mass index (BMI). DESIGN AND METHODS: We conducted a genome-wide linkage scan and regional association study WC and BMI among 633 Chinese families. 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 6 single nucleotide polymorphisms (SNPs) at 2p24.3–2q12.2 (rs100955, rs13020676, rs13014034, rs12990515, rs17024325 and rs2192712) and 5 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: We described genomic regions on chromosomes 2, 6, and 22 which may harbor important obesity-susceptibility loci. Follow-up study of these regions revealed several novel variants associated with obesity related traits. Future work to confirm these promising findings is warranted.