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

Authors: ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Lai, Chao Qiang; Parnell, Laurence; LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEN, JIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RICHARDSON, KRIS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, DUO - Zhejiang University; ARNETT, DONNA - University Of Alabama; BORECKI, INGRID - Washington University; ZHENG, JU-SHENG - Zhejian University

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2014
Publication Date: 9/11/2014
Citation: Ordovas, J., Lai, C., Parnell, L.D., Lee, Y., Shen, J., Smith, C.E., Richardson, K., Li, D., Arnett, D.K., Borecki, I.B., Zheng, J. 2014. Genome-wide interaction of genotype by erythrocyte n-3 PUFAs contributes to phenotypic variance of diabetes-related traits. Biomed Central (BMC) Genomics. 15:781. https://doi.org/10.1186/1471-2164-15-781.
DOI: https://doi.org/10.1186/1471-2164-15-781

Interpretive Summary: Type 2 diabetes (T2D) is one of the most common chronic diseases reducing the quality of life and healthy aging because the cells in the body cannot use insulin properly, resulting in insulin resistance. Ability to maintain blood sugar levels depends on an individual’s genetic makeup and diet and lifestyle habits. Scientists thought that dietary fats and genetic makeup of some individuals influence insulin resistance and T2D. Our study confirmed that fats affect fasting insulin levels and insulin resistance in about one quarter of the population.

Technical Abstract: While genome-wide association studies (GWAS) and candidate gene approach have identified many genetic variants that contribute to disease risk as main effects, the impact of genotype by environment (GxE) interactions remains rather under-surveyed. The present study aimed to examine variance contribution of genotype by environment (GxE) interaction for different types of erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a white population living in the U.S. (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 insulin, glucose and adiponectin. GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Docosapentaenoic acid contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal=0.034) and insulin (24.3%, P-nominal=0.042). Arachidonic acid/(eicosapentaenoic acid+docosahexaenoic acid) ratio contributed the most significant GxE variance to the total variance of glucose (27.0%, P-nominal=0.023). GxE variance of arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal=0.058). For each trait, GxE GWAS identified a larger number of significant single-nucleotide polymorphisms (SNP) (P-interaction=10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In conclusion, erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level. Different n-3 fatty acids showed various GxE patterns.