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).
  
  
  CONCLUSIONS
  Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Zheng
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Patricia
authors.initials: P
authors.lastname: Casas-Agustench
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: Noel
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. jose.ordovas@tufts.edu.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3