title: Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.
abstract: OBJECTIVE
  Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.
  
  
  METHODS
  Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant.
  
  
  RESULTS
  Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele.
  
  
  CONCLUSIONS
  Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.
authors.affiliation: Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center, Houston, Houston, Texas, USA. jennifer.a.nettleton@uth.tmc.edu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Nettleton
authors.forename: Nicola M
authors.initials: NM
authors.lastname: McKeown
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kanoni
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.forename: Julius
authors.initials: J
authors.lastname: Ngwa
authors.forename: Frank J A
authors.initials: FJ
authors.lastname: van Rooij
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ye
authors.forename: Tosh
authors.initials: T
authors.lastname: Tanaka
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Anderson
authors.forename: Jack L
authors.initials: JL
authors.lastname: Follis
authors.forename: Luc
authors.initials: L
authors.lastname: Djousse
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mukamal
authors.forename: Constantina
authors.initials: C
authors.lastname: Papoutsakis
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Mary F
authors.initials: MF
authors.lastname: Feitosa
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Tamara
authors.initials: T
authors.lastname: Harris
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Denise K
authors.initials: DK
authors.lastname: Houston
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
authors.forename: Lenore
authors.initials: L
authors.lastname: Launer
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Loos
authors.forename: Michael
authors.initials: M
authors.lastname: Nalls
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Frida
authors.initials: F
authors.lastname: Renstrom
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rice
authors.forename: Ulf
authors.initials: U
authors.lastname: Riserus
authors.forename: Olov
authors.initials: O
authors.lastname: Rolandsson
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Georgia
authors.initials: G
authors.lastname: Saylor
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Per
authors.initials: P
authors.lastname: Sjogren
authors.forename: Albert
authors.initials: A
authors.lastname: Smith
authors.forename: Laufey
authors.initials: L
authors.lastname: Steingrímsdóttir
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: George V
authors.initials: GV
authors.lastname: Dedoussis
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: L  Adrienne
authors.initials: L
authors.lastname: Cupples
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D002523:Edible Grain; D005215:Fasting / Q000097:blood*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin