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

Laura Kelly Vaughan; Howard W. Wiener; Stella Aslibekyan; David B. Allison; Peter J. Havel; Kimber L. Stanhope; Diane M. O'Brien; Scarlett E. Hopkins; Dominick J. Lemas; Bert B. Boyer; Hemant K. Tiwari

doi:10.1016/j.metabol.2015.02.008

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

Laura Kelly Vaughan, Howard W. Wiener, Stella Aslibekyan, David B. Allison, Peter J. Havel, Kimber L. Stanhope, Diane M. O'Brien, Scarlett E. Hopkins, Dominick J. Lemas, Bert B. Boyer, Hemant K. Tiwari

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	689-697
Number of pages	9
Journal	Metabolism: Clinical and Experimental
Volume	64
Issue number	6
DOIs	https://doi.org/10.1016/j.metabol.2015.02.008
State	Published - Jun 1 2015
Externally published	Yes

Keywords

Alaska Native
Linkage
Obesity
n-3 fatty acids

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

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10.1016/j.metabol.2015.02.008

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Vaughan, L. K., Wiener, H. W., Aslibekyan, S., Allison, D. B., Havel, P. J., Stanhope, K. L., O'Brien, D. M., Hopkins, S. E., Lemas, D. J., Boyer, B. B., & Tiwari, H. K. (2015). 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. Metabolism: Clinical and Experimental, 64(6), 689-697. https://doi.org/10.1016/j.metabol.2015.02.008

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. / Vaughan, Laura Kelly; Wiener, Howard W.; Aslibekyan, Stella et al.
In: Metabolism: Clinical and Experimental, Vol. 64, No. 6, 01.06.2015, p. 689-697.

Research output: Contribution to journal › Article › peer-review

Vaughan, LK, Wiener, HW, Aslibekyan, S, Allison, DB, Havel, PJ, Stanhope, KL, O'Brien, DM, Hopkins, SE, Lemas, DJ, Boyer, BB & Tiwari, HK 2015, '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', Metabolism: Clinical and Experimental, vol. 64, no. 6, pp. 689-697. https://doi.org/10.1016/j.metabol.2015.02.008

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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",

abstract = "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.",

keywords = "Alaska Native, Linkage, Obesity, n-3 fatty acids",

author = "Vaughan, {Laura Kelly} and Wiener, {Howard W.} and Stella Aslibekyan and Allison, {David B.} and Havel, {Peter J.} and Stanhope, {Kimber L.} and O'Brien, {Diane M.} and Hopkins, {Scarlett E.} and Lemas, {Dominick J.} and Boyer, {Bert B.} and Tiwari, {Hemant K.}",

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T1 - 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

AU - Vaughan, Laura Kelly

AU - Wiener, Howard W.

AU - Aslibekyan, Stella

AU - Allison, David B.

AU - Havel, Peter J.

AU - Stanhope, Kimber L.

AU - O'Brien, Diane M.

AU - Hopkins, Scarlett E.

AU - Lemas, Dominick J.

AU - Boyer, Bert B.

AU - Tiwari, Hemant K.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

KW - Alaska Native

KW - Linkage

KW - Obesity

KW - n-3 fatty acids

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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

Abstract

Keywords

ASJC Scopus subject areas

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