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Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

TitleGene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.
Publication TypeJournal Article
Year of Publication2015
AuthorsNettleton JA, Follis JL, Ngwa JS, Smith CE, Ahmad S, Tanaka T, Wojczynski MK, Voortman T, Lemaitre RN, Kristiansson K, Nuotio M-L, Houston DK, Perälä M-M, Qi Q, Sonestedt E, Manichaikul A, Kanoni S, Ganna A, Mikkilä V, North KE, Siscovick DS, Harald K, McKeown NM, Johansson I, Rissanen H, Liu Y, Lahti J, Hu FB, Bandinelli S, Rukh G, Rich S, Booij L, Dmitriou M, Ax E, Raitakari O, Mukamal K, Männisto S, Hallmans G, Jula A, Ericson U, Jacobs DR, van Rooij FJA, Deloukas P, Sjogren P, Kähönen M, Djoussé L, Perola M, Barroso I, Hofman A, Stirrups K, Viikari J, Uitterlinden AG, Kalafati IP, Franco OH, Mozaffarian D, Salomaa V, Borecki IB, Knekt P, Kritchevsky SB, Eriksson JG, Dedoussis GV, Qi L, Ferrucci L, Orho-Melander M, Zillikens CM, Ingelsson E, Lehtimäki T, Renstrom F, L Cupples A, Loos RJF
Secondary AuthorsFranks PW
JournalHum Mol Genet
Volume24
Issue16
Pagination4728-38
Date Published2015 Aug 15
ISSN1460-2083
KeywordsAdult, Body Mass Index, Case-Control Studies, Diet, Western, Epistasis, Genetic, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Obesity, Polymorphism, Single Nucleotide
Abstract

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

DOI10.1093/hmg/ddv186
Alternate JournalHum Mol Genet
PubMed ID25994509
PubMed Central IDPMC4512626
Grant ListHL073168 / HL / NHLBI NIH HHS / United States
HL34594 / HL / NHLBI NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01-HL-088215 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
N01-AG-6-2101 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
R01-AG032098 / AG / NIA NIH HHS / United States
R01-DK-8925601 / DK / NIDDK NIH HHS / United States
N02‐HL‐6‐4278 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01-AG-6-2103 / AG / NIA NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
263 MD 821336 / MD / NIMHD NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
CA87969 / CA / NCI NIH HHS / United States
DK58845 / DK / NIDDK NIH HHS / United States
HL088521 / HL / NHLBI NIH HHS / United States
5K01DK082729-04 / DK / NIDDK NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
U01HG004399 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
WT098051 / / Wellcome Trust / United Kingdom
HHSN268201100010C / / PHS HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
P30 DK046200 / DK / NIDDK NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01-HC-95164 / HC / NHLBI NIH HHS / United States
R01HL105756 / HL / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
R01-HL-087700 / HL / NHLBI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
R01AG023629 / AG / NIA NIH HHS / United States
R01-DK-075681 / DK / NIDDK NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
N01-AG-6-2106 / AG / NIA NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
R01HL087652 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
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HHSN268201200036C / / PHS HHS / United States
HHSN268200782096C / / PHS HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
R01HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
HL071981 / HL / NHLBI NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
263 MD 9164 / MD / NIMHD NIH HHS / United States
DK080140 / DK / NIDDK NIH HHS / United States
89061/Z/09/Z / / Wellcome Trust / United Kingdom
K08 HL112845 / HL / NHLBI NIH HHS / United States
K01 AG030506 / AG / NIA NIH HHS / United States
DK46200 / DK / NIDDK NIH HHS / United States
089062/Z/09/Z / / Wellcome Trust / United Kingdom
N01-HC-95167 / HC / NHLBI NIH HHS / United States
R01HL120393 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States