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Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.
|Title||Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Vaughan, LKelly, Wiener, HW, Aslibekyan, S, Allison, DB, Havel, PJ, Stanhope, KL, O'Brien, DM, Hopkins, SE, Lemas, DJ, Boyer, BB, Tiwari, HK|
|Date Published||2015 Jun|
OBJECTIVE: To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people.
MATERIAL AND METHODS: We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks.
RESULTS: We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004).
CONCLUSIONS: This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people.
|Alternate Journal||Metab. Clin. Exp.|
|PubMed Central ID||PMC4408244|
|Grant List||K01 DK080188 / DK / NIDDK NIH HHS / United States |
P20 RR016430 / RR / NCRR NIH HHS / United States
P30 DK056336 / DK / NIDDK NIH HHS / United States
P30 GM103325 / GM / NIGMS NIH HHS / United States
R01 DK074842 / DK / NIDDK NIH HHS / United States