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Genome‐wide linkage and regional association study of obesity‐related phenotypes: The GenSalt study
Author(s) -
Liu Angela Y.,
Gu Dongfeng,
Hixson James E.,
Rao Dabeeru C.,
Shimmin Lawrence C.,
Jaquish Cashell E.,
Liu DePei,
He Jiang,
Kelly Tanika N.
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20469
Subject(s) - single nucleotide polymorphism , quantitative trait locus , genetics , linkage (software) , body mass index , genetic linkage , genetic association , waist , obesity , biology , phenotype , gene , genotype , endocrinology
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.