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  • Title: Genome-wide linkage and regional association study of obesity-related phenotypes: the GenSalt study.
    Author: Liu AY, Gu D, Hixson JE, Rao DC, Shimmin LC, Jaquish CE, Liu DP, He J, Kelly TN.
    Journal: Obesity (Silver Spring); 2014 Feb; 22(2):545-56. PubMed ID: 23526746.
    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.
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