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

Nettleton, Jennifer A ; Follis, Jack L ; Ngwa, Julius S ; Smith, Caren E ; Ahmad, Shafqat LU ; Tanaka, Toshiko ; Wojczynski, Mary K ; Voortman, Trudy ; Lemaitre, Rozenn N and Kristiansson, Kati LU , et al. (2015) In Human Molecular Genetics 24(16). p.4728-4738
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. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) 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, fried potatoes (unfavorable). Multi-variable adjusted, linear regression within each cohort, followed by inverse... (More)
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. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) 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, fried potatoes (unfavorable). Multi-variable 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; 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
24
issue
16
pages
4728 - 4738
publisher
Oxford University Press
external identifiers
  • pmid:25994509
  • wos:000361315400020
  • scopus:84939502098
  • pmid:25994509
ISSN
0964-6906
DOI
10.1093/hmg/ddv186
language
English
LU publication?
yes
id
5b355815-61a9-4e9a-9964-a4bc55155fe6 (old id 5448437)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25994509?dopt=Abstract
date added to LUP
2016-04-01 09:56:31
date last changed
2025-04-04 14:29:19
@article{5b355815-61a9-4e9a-9964-a4bc55155fe6,
  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. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) 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, fried potatoes (unfavorable). Multi-variable 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; 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.}},
  author       = {{Nettleton, Jennifer A and Follis, Jack L and Ngwa, Julius S and Smith, Caren E and Ahmad, Shafqat and Tanaka, Toshiko and Wojczynski, Mary K and Voortman, Trudy and Lemaitre, Rozenn N and Kristiansson, Kati and Nuotio, Marja-Liisa and Houston, Denise K and Perälä, Mia-Maria and Qi, Qibin and Sonestedt, Emily and Manichaikul, Ani and Kanoni, Stavroula and Ganna, Andrea and Mikkilä, Vera and North, Kari E and Siscovick, David S and Harald, Kennet and McKeown, Nicola M and Johansson, Ingegerd and Rissanen, Harri and Liu, Yongmei and Lahti, Jari and Hu, Frank B and Bandinelli, Stefania and Rukh, Gull and Rich, Stephen and Booij, Lisanne and Dmitriou, Maria and Ax, Erika and Raitakari, Olli and Mukamal, Kenneth and Männistö, Satu and Hallmans, Göran and Jula, Antti and Ericson, Ulrika and Jacobs, David R and van Rooij, Frank J A and Deloukas, Panos and Sjögren, Per and Kähönen, Mika and Djousse, Luc and Perola, Markus and Barroso, Inês and Hofman, Albert and Stirrups, Kathleen and Viikari, Jorma and Uitterlinden, André G and Kalafati, Ioanna P and Franco, Oscar H and Mozaffarian, Dariush and Salomaa, Veikko and Borecki, Ingrid B and Knekt, Paul and Kritchevsky, Stephen B and Eriksson, Johan G and Dedoussis, George V and Qi, Lu and Ferrucci, Luigi and Orho-Melander, Marju and Zillikens, M Carola and Ingelsson, Erik and Lehtimäki, Terho and Renström, Frida and Cupples, L Adrienne and Loos, Ruth and Franks, Paul}},
  issn         = {{0964-6906}},
  language     = {{eng}},
  number       = {{16}},
  pages        = {{4728--4738}},
  publisher    = {{Oxford University Press}},
  series       = {{Human Molecular Genetics}},
  title        = {{Gene×dietary pattern interactions in obesity: analysis of up to 68,317 adults of European ancestry.}},
  url          = {{http://dx.doi.org/10.1093/hmg/ddv186}},
  doi          = {{10.1093/hmg/ddv186}},
  volume       = {{24}},
  year         = {{2015}},
}