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

Authors

• Caren E. Smith, USDA Human Nutrition Research
• Jack L. Follis, University of St. Thomas
• Hassan S. Dashti, Massachusetts General Hospital
• Toshiko Tanaka, National Institute on Aging
• Mariaelisa Graff, The University of North Carolina at Chapel Hill
• Amanda M. Fretts, University of Washington
• Tuomas O. Kilpeläinen, University of Copenhagen, Denmark
• Mary K. Wojczynski, Washington University in St. Louis
• Kris Richardson, USDA Human Nutrition Research Center on Aging
• Mike A. Nalls, National Institute on Aging
• Christina-Alexandra Schulz, Lund University, Sweden
• Yongmei Liu, Wake Forest University
• Alexis C. Frazier-Wood, USDA Agricultural Research Service
• Esther van Eekelen, Leiden University, The Netherlands
• Carol Wang, University of Western Australia, Australia
• Paul S. de Vries, University of Texas Health Science Center at Houston
• Vera Mikkilä, University of Helsinki, Finland
• Rebecca Rohde, The University of North Carolina at Chapel Hill
• Bruce M. Psaty, University of Washington
• Torben Hansen, University of Copenhagen, Denmark
• Mary F. Feitosa, Washington University in St. Louis
• Chao-Qiang Lai, USDA Agricultural Research Service
• Denise K. Houston, Wake Forest University
• Luigi Ferruci, National Institute on Aging
• Ulrika Ericson, Lund University, Sweden
• Zhe Wang, University of Texas Health Science Center at Houston
• Renée de Mutsert, Leiden University, The Netherlands
• Wendy H. Oddy, University of Tasmania, Australia
• Ester A. L. de Jonge, University Medical Center, The Netherlands
• Ilkka Seppälä, Tampere University, Finland
• Donna K. Arnett, University of KentuckyFollow

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.

Document Type

Article

Publication Date

2-2018

Notes/Citation Information

Published in Molecular Nutrition & Food Research, v. 62, issue 3, 1700347, p. 1-27.

© 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

The copyright holder has granted the permission for posting the article here.

This is the peer reviewed version of the following article: Smith, C. E., Follis, J. L., Dashti, H. S., Tanaka, T., Graff, M., Fretts, A. M., ... Ordovás, J. M. (2018). Genome-wide interactions with dairy intake for body mass index in adults of European descent. Molecular Nutrition & Food Research, 62(3), 1700347, which has been published in final form at https://doi.org/10.1002/mnfr.201700347. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article or visit: https://doi.org/10.1002/mnfr.201700347

Digital Object Identifier (DOI)

https://doi.org/10.1002/mnfr.201700347

Funding Information

Complete funding information is located in the Supporting Information, Table 8. B. P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. M. N.’ participation is supported by a consulting contract between Kelly Services and the National Institute on Aging, NIH, Bethesda, MD, USA.

Related Content

Supporting Information is available from the Wiley Online Library or from the author.

Repository Citation

Smith, Caren E.; Follis, Jack L.; Dashti, Hassan S.; Tanaka, Toshiko; Graff, Mariaelisa; Fretts, Amanda M.; Kilpeläinen, Tuomas O.; Wojczynski, Mary K.; Richardson, Kris; Nalls, Mike A.; Schulz, Christina-Alexandra; Liu, Yongmei; Frazier-Wood, Alexis C.; van Eekelen, Esther; Wang, Carol; de Vries, Paul S.; Mikkilä, Vera; Rohde, Rebecca; Psaty, Bruce M.; Hansen, Torben; Feitosa, Mary F.; Lai, Chao-Qiang; Houston, Denise K.; Ferruci, Luigi; Ericson, Ulrika; Wang, Zhe; de Mutsert, Renée; Oddy, Wendy H.; de Jonge, Ester A. L.; Seppälä, Ilkka; and Arnett, Donna K., "Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent" (2018). Epidemiology and Environmental Health Faculty Publications. 61.
https://uknowledge.uky.edu/epidemiology_facpub/61