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

Angela Y. Liu, Dongfeng Gu, James E. Hixson, Dabeeru C. Rao, Lawrence C. Shimmin, Cashell E. Jaquish, De Pei Liu, Jiang He, Tanika N. Kelly

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)545-556
Number of pages12
JournalObesity
Volume22
Issue number2
DOIs
StatePublished - Feb 2014

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