Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Caren E Smith, Jack L Follis, Hassan S Dashti, Toshiko Tanaka, Mariaelisa Graff, Amanda M Fretts, Tuomas O. Kilpeläinen, Mary K Wojczynski, Kris Richardson, Mike A Nalls, Christina-Alexandra Schulz, Yongmei Liu, Alexis C Frazier-Wood, Esther van Eekelen, Carol Wang, Paul S de Vries, Vera Mikkilä, Rebecca Rohde, Bruce M Psaty, Torben HansenMary F Feitosa, Chao-Qiang Lai, Denise K Houston, Luigi Ferruci, Ulrika Ericson, Zhe Wang, Renée de Mutsert, Wendy H Oddy, Ester A L de Jonge, Ilkka Seppälä, Anne E Justice, Rozenn N Lemaitre, Thorkild I.A. Sørensen, Michael A Province, Laurence D Parnell, Melissa E Garcia, Stefania Bandinelli, Marju Orho-Melander, Stephen S Rich, Frits R Rosendaal, Craig E Pennell, Jessica C Kiefte-de Jong, Mika Kähönen, Kristin L Young, Oluf Pedersen, Stella Aslibekyan, Jerome I Rotter, Dennis O Mook-Kanamori, M Carola Zillikens, Olli T Raitakari, Kari E North, Kim Overvad, Donna K Arnett, Albert Hofman, Terho Lehtimäki, Anne Tjønneland, André G Uitterlinden, Fernando Rivadeneira, Oscar H Franco, J Bruce German, David S Siscovick, L Adrienne Cupples, José M Ordovás

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8 Citationer (Scopus)

Abstract

SCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.

METHODS AND RESULTS: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10-7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3' of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10-8)such that each serving of low-fat dairy was associated with 0.225 kg m-2lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure.

CONCLUSION: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.

OriginalsprogEngelsk
Artikelnummer1700347
TidsskriftMolecular Nutrition & Food Research
Vol/bind62
Udgave nummer3
Sider (fra-til)1-12
Antal sider12
ISSN1613-4125
DOI
StatusUdgivet - 2018

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