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 Hansen; Mary 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

doi:10.1002/mnfr.201700347

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

Mol Nutr Food Res. 2018 Feb;62(3):10.1002/mnfr.201700347. doi: 10.1002/mnfr.201700347. Epub 2017 Dec 11.

Authors

Caren E Smith¹, Jack L Follis², Hassan S Dashti^{3

4}, Toshiko Tanaka⁵, Mariaelisa Graff⁶, Amanda M Fretts⁷, Tuomas O Kilpeläinen⁸, Mary K Wojczynski⁹, Kris Richardson¹⁰, Mike A Nalls^{11

12}, Christina-Alexandra Schulz¹³, Yongmei Liu¹⁴, Alexis C Frazier-Wood¹⁵, Esther van Eekelen¹⁶, Carol Wang¹⁷, Paul S de Vries^{18

19}, Vera Mikkilä^{20

21}, Rebecca Rohde⁶, Bruce M Psaty^{22

23}, Torben Hansen⁸, Mary F Feitosa⁹, Chao-Qiang Lai²⁴, Denise K Houston²⁵, Luigi Ferruci⁵, Ulrika Ericson¹³, Zhe Wang²⁶, Renée de Mutsert¹⁶, Wendy H Oddy²⁷, Ester A L de Jonge^{19

28}, Ilkka Seppälä²⁹, Anne E Justice⁶, Rozenn N Lemaitre³⁰, Thorkild I A Sørensen^{8

31

32}, Michael A Province⁹, Laurence D Parnell²⁴, Melissa E Garcia³³, Stefania Bandinelli³⁴, Marju Orho-Melander¹³, Stephen S Rich³⁵, Frits R Rosendaal¹⁶, Craig E Pennell¹⁷, Jessica C Kiefte-de Jong¹⁹, Mika Kähönen³⁶, Kristin L Young⁶, Oluf Pedersen⁸, Stella Aslibekyan³⁷, Jerome I Rotter³⁸, Dennis O Mook-Kanamori^{16

39}, M Carola Zillikens²⁸, Olli T Raitakari^{21

40}, Kari E North^{6

41}, Kim Overvad^{42

43}, Donna K Arnett⁴⁴, Albert Hofman^{19

45}, Terho Lehtimäki²⁹, Anne Tjønneland⁴⁶, André G Uitterlinden²⁸, Fernando Rivadeneira^{28

47}, Oscar H Franco¹⁹, J Bruce German⁴⁸, David S Siscovick⁴⁹, L Adrienne Cupples⁵⁰, José M Ordovás^{1

51

52}

Affiliations

¹ Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
² University of St Thomas, Houston, TX, USA.
³ Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
⁴ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁵ Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁶ Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁷ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁸ Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
⁹ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
¹⁰ Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
¹¹ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
¹² Contractor/consultant with Kelly Services, Rockville, MD, USA.
¹³ LUDC, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
¹⁴ Department of Epidemiology & Prevention, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
¹⁵ USDA / ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.
¹⁶ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁷ School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
¹⁸ Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁹ Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
²⁰ Division of Nutrition, Department of Food and Environmental Sciences, University of Helsinki, Helsinki.
²¹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
²² Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA.
²³ Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
²⁴ USDA ARS, Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
²⁵ Department of Internal Medicine, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
²⁶ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
²⁷ Menzies Institute for Medical Research, University of Tasmania, Australia.
²⁸ Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
²⁹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere University School of Medicine, Tampere, Finland.
³⁰ Department of Medicine, University of Washington, Seattle, WA, USA.
³¹ Department of Clinical Epidemiology (formerly Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, 2000, Denmark.
³² MRC Integrative Epidemiology Unit & School of Social and community Medicine, University of Bristol, Bristol, BS82BN, UK.
³³ National Institute of Aging, Bethesda, MD, USA.
³⁴ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
³⁵ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
³⁶ Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
³⁷ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁸ Institute for Translational Genomics and Population Sciences Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
³⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
⁴⁰ Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku, Finland.
⁴¹ Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, 27514, USA.
⁴² Department of Public Health, Section for Epidemiology, Aarhus University, DK-8000, Aarhus C, Denmark.
⁴³ Aalborg University Hospital, DK-9000, Aalborg, Denmark.
⁴⁴ College of Public Health, University of Kentucky, Lexington, KY, USA.
⁴⁵ Department of Nutrition, Harvard School of Public Health, Boston, USA.
⁴⁶ Danish Cancer Society Research Center, Copenhagen, 2100, Denmark.
⁴⁷ Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the Netherlands.
⁴⁸ Department of Food Science and Technology, University of California, Davis, CA, USA.
⁴⁹ New York Academy of Medicine, New York, NY, USA.
⁵⁰ Department of Biostatistics, Boston University School of Public Health, Boston, USA.
⁵¹ The Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC) Madrid, Spain.
⁵² IMDEA Food, Madrid, Spain.

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.

Keywords: CHARGE consortium; body mass index; dairy intake; genome-wide interaction study; meta-analysis.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Adult
Aged
Body Mass Index*
Cohort Studies
Cross-Sectional Studies
Dairy Products*
Female
Gene Frequency
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Myosin-Light-Chain Phosphatase / genetics
Polymorphism, Single Nucleotide*
White People / genetics

Substances

ACTA2 protein, human
Actins
Myosin-Light-Chain Phosphatase
PPP1R12A protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding