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.
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.
Nettleton
Jennifer A
JA
Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center, Houston, Houston, Texas, USA. jennifer.a.nettleton@uth.tmc.edu
McKeown
Nicola M
NM
Kanoni
Stavroula
S
Lemaitre
Rozenn N
RN
Hivert
Marie-France
MF
Ngwa
Julius
J
van Rooij
Frank J A
FJ
Sonestedt
Emily
E
Wojczynski
Mary K
MK
Ye
Zheng
Z
Tanaka
Tosh
T
Garcia
Melissa
M
Anderson
Jennifer S
JS
Follis
Jack L
JL
Djousse
Luc
L
Mukamal
Kenneth
K
Papoutsakis
Constantina
C
Mozaffarian
Dariush
D
Zillikens
M Carola
MC
Bandinelli
Stefania
S
Bennett
Amanda J
AJ
Borecki
Ingrid B
IB
Feitosa
Mary F
MF
Ferrucci
Luigi
L
Forouhi
Nita G
NG
Groves
Christopher J
CJ
Hallmans
Goran
G
Harris
Tamara
T
Hofman
Albert
A
Houston
Denise K
DK
Hu
Frank B
FB
Johansson
Ingegerd
I
Kritchevsky
Stephen B
SB
Langenberg
Claudia
C
Launer
Lenore
L
Liu
Yongmei
Y
Loos
Ruth J
RJ
Nalls
Michael
M
Orho-Melander
Marju
M
Renstrom
Frida
F
Rice
Kenneth
K
Riserus
Ulf
U
Rolandsson
Olov
O
Rotter
Jerome I
JI
Saylor
Georgia
G
Sijbrands
Eric J G
EJ
Sjogren
Per
P
Smith
Albert
A
Steingrímsdóttir
Laufey
L
Uitterlinden
André G
AG
Wareham
Nicholas J
NJ
Prokopenko
Inga
I
Pankow
James S
JS
van Duijn
Cornelia M
CM
Florez
Jose C
JC
Witteman
Jacqueline C M
JC
Dupuis
Josée
J
Dedoussis
George V
GV
Ordovas
Jose M
JM
Ingelsson
Erik
E
Cupples
L  Adrienne
L
Siscovick
David S
DS
Franks
Paul W
PW
Meigs
James B
JB
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
D001786:Blood Glucose; D007328:Insulin