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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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−2 lower 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.

Original languageEnglish
Article number1700347
JournalMolecular Nutrition and Food Research
Volume62
Issue number3
DOIs
StatePublished - Feb 1 2018

Keywords

  • CHARGE consortium
  • body mass index
  • dairy intake
  • genome-wide interaction study
  • meta-analysis

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