Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits

Ju Sheng Zheng; Chao Qiang Lai; Laurence D. Parnell; Yu Chi Lee; Jian Shen; Caren E. Smith; Patricia Casas-Agustench; Kris Richardson; Duo Li; Sabrina E. Noel; Katherine L. Tucker; Donna K. Arnett; Ingrid B. Borecki; José M. Ordovás

doi:10.1186/1471-2164-15-781

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits

Ju Sheng Zheng, Chao Qiang Lai, Laurence D. Parnell, Yu Chi Lee, Jian Shen, Caren E. Smith, Patricia Casas-Agustench, Kris Richardson, Duo Li, Sabrina E. Noel, Katherine L. Tucker, Donna K. Arnett, Ingrid B. Borecki, José M. Ordovás

College of Public Health

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

6 Scopus citations

Abstract

Background: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). Results: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033).Conclusion: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

Original language	English
Article number	781
Journal	BMC Genomics
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/1471-2164-15-781
State	Published - Sep 11 2014

Bibliographical note

Funding Information:
This study was funded by the National Natural Science Foundation of China (NSFC, No. 81273054); by the National Basic Research Program of China (973 Program: 2011CB504002); by NIH grants HL54776, HL078885, P01AG023394, and P50HL105185; by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture, Agriculture Research Service; by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIOF-GA-2010-272581. The authors are grateful to Health Diagnostic Laboratory, Inc. (Richmond, VA) for performing the RBC fatty acid profiles from the BPRHS. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. The USDA is an equal opportunity provider and employer. No potential conflicts of interest relevant to this article were reported.

Publisher Copyright:
© 2014 Zheng et al.; licensee BioMed Central Ltd.

ASJC Scopus subject areas

Biotechnology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/1471-2164-15-781

Cite this

Zheng, J. S., Lai, C. Q., Parnell, L. D., Lee, Y. C., Shen, J., Smith, C. E., Casas-Agustench, P., Richardson, K., Li, D., Noel, S. E., Tucker, K. L., Arnett, D. K., Borecki, I. B., & Ordovás, J. M. (2014). Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits. BMC Genomics, 15(1), [781]. https://doi.org/10.1186/1471-2164-15-781

@article{0a54fa061a7145d3ab7ab57fa5f11571,

title = "Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits",

abstract = "Background: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). Results: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033).Conclusion: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.",

author = "Zheng, {Ju Sheng} and Lai, {Chao Qiang} and Parnell, {Laurence D.} and Lee, {Yu Chi} and Jian Shen and Smith, {Caren E.} and Patricia Casas-Agustench and Kris Richardson and Duo Li and Noel, {Sabrina E.} and Tucker, {Katherine L.} and Arnett, {Donna K.} and Borecki, {Ingrid B.} and Ordov{\'a}s, {Jos{\'e} M.}",

note = "Funding Information: This study was funded by the National Natural Science Foundation of China (NSFC, No. 81273054); by the National Basic Research Program of China (973 Program: 2011CB504002); by NIH grants HL54776, HL078885, P01AG023394, and P50HL105185; by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture, Agriculture Research Service; by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIOF-GA-2010-272581. The authors are grateful to Health Diagnostic Laboratory, Inc. (Richmond, VA) for performing the RBC fatty acid profiles from the BPRHS. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. The USDA is an equal opportunity provider and employer. No potential conflicts of interest relevant to this article were reported. Publisher Copyright: {\textcopyright} 2014 Zheng et al.; licensee BioMed Central Ltd.",

year = "2014",

month = sep,

day = "11",

doi = "10.1186/1471-2164-15-781",

language = "English",

volume = "15",

number = "1",

}

Zheng, JS, Lai, CQ, Parnell, LD, Lee, YC, Shen, J, Smith, CE, Casas-Agustench, P, Richardson, K, Li, D, Noel, SE, Tucker, KL, Arnett, DK, Borecki, IB & Ordovás, JM 2014, 'Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits', BMC Genomics, vol. 15, no. 1, 781. https://doi.org/10.1186/1471-2164-15-781

TY - JOUR

T1 - Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits

AU - Zheng, Ju Sheng

AU - Lai, Chao Qiang

AU - Parnell, Laurence D.

AU - Lee, Yu Chi

AU - Shen, Jian

AU - Smith, Caren E.

AU - Casas-Agustench, Patricia

AU - Richardson, Kris

AU - Li, Duo

AU - Noel, Sabrina E.

AU - Tucker, Katherine L.

AU - Arnett, Donna K.

AU - Borecki, Ingrid B.

AU - Ordovás, José M.

N1 - Funding Information: This study was funded by the National Natural Science Foundation of China (NSFC, No. 81273054); by the National Basic Research Program of China (973 Program: 2011CB504002); by NIH grants HL54776, HL078885, P01AG023394, and P50HL105185; by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture, Agriculture Research Service; by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIOF-GA-2010-272581. The authors are grateful to Health Diagnostic Laboratory, Inc. (Richmond, VA) for performing the RBC fatty acid profiles from the BPRHS. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. The USDA is an equal opportunity provider and employer. No potential conflicts of interest relevant to this article were reported. Publisher Copyright: © 2014 Zheng et al.; licensee BioMed Central Ltd.

PY - 2014/9/11

Y1 - 2014/9/11

N2 - Background: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). Results: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033).Conclusion: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

AB - Background: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). Results: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033).Conclusion: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

UR - http://www.scopus.com/inward/record.url?scp=84907287778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907287778&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-15-781

DO - 10.1186/1471-2164-15-781

M3 - Article

C2 - 25213455

AN - SCOPUS:84907287778

VL - 15

IS - 1

M1 - 781

ER -

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this