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

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

College of Public Health

Research output: Contribution to journal › Article › peer-review

9 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 language	English
Article number	1700347
Journal	Molecular Nutrition and Food Research
Volume	62
Issue number	3
DOIs	https://doi.org/10.1002/mnfr.201700347
State	Published - Feb 1 2018

Bibliographical note

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funding

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. Young Finns Study: The expert technical assistance in the statistical analyses by Irina Lisinen and Mika Helminen is gratefully acknowledged.

Funders	Funder number
Contractor/consultant with Kelly Services
National Institutes of Health (NIH)
National Institute on Aging
National Center for Advancing Translational Sciences (NCATS)	KL2TR001109
National Center for Advancing Translational Sciences (NCATS)

Keywords

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

ASJC Scopus subject areas

Biotechnology
Food Science

Access to Document

10.1002/mnfr.201700347

Cite this

Smith, C. E., Follis, J. L., Dashti, H. S., Tanaka, T., Graff, M., Fretts, A. M., Kilpeläinen, T. O., Wojczynski, M. K., Richardson, K., Nalls, M. A., Schulz, C. A., Liu, Y., Frazier-Wood, A. C., van Eekelen, E., Wang, C., de Vries, P. S., Mikkilä, V., Rohde, R., Psaty, B. M., ... Ordovás, J. M. (2018). Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent. Molecular Nutrition and Food Research, 62(3), Article 1700347. https://doi.org/10.1002/mnfr.201700347

@article{39abb69a78314bf1b10a1ffde664a5c4,

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

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{\textquoteright} 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",

author = "Smith, \{Caren E.\} and Follis, \{Jack L.\} and Dashti, \{Hassan S.\} and Toshiko Tanaka and Mariaelisa Graff and Fretts, \{Amanda M.\} and Kilpel{\"a}inen, \{Tuomas O.\} and Wojczynski, \{Mary K.\} and Kris Richardson and Nalls, \{Mike A.\} and Schulz, \{Christina Alexandra\} and Yongmei Liu and Frazier-Wood, \{Alexis C.\} and \{van Eekelen\}, Esther and Carol Wang and \{de Vries\}, \{Paul S.\} and Vera Mikkil{\"a} and Rebecca Rohde and Psaty, \{Bruce M.\} and Torben Hansen and Feitosa, \{Mary F.\} and Lai, \{Chao Qiang\} and Houston, \{Denise K.\} and Luigi Ferruci and Ulrika Ericson and Zhe Wang and \{de Mutsert\}, Ren{\'e}e and Oddy, \{Wendy H.\} and \{de Jonge\}, \{Ester A.L.\} and Ilkka Sepp{\"a}l{\"a} and Justice, \{Anne E.\} and Lemaitre, \{Rozenn N.\} and S{\o}rensen, \{Thorkild I.A.\} and Province, \{Michael A.\} and Parnell, \{Laurence D.\} and Garcia, \{Melissa E.\} and Stefania Bandinelli and Marju Orho-Melander and Rich, \{Stephen S.\} and Rosendaal, \{Frits R.\} and Pennell, \{Craig E.\} and \{Kiefte-de Jong\}, \{Jessica C.\} and Mika K{\"a}h{\"o}nen and Young, \{Kristin L.\} and Oluf Pedersen and Stella Aslibekyan and Rotter, \{Jerome I.\} and Mook-Kanamori, \{Dennis O.\} and Zillikens, \{M. Carola\} and Raitakari, \{Olli T.\} and North, \{Kari E.\} and Kim Overvad and Arnett, \{Donna K.\} and Albert Hofman and Terho Lehtim{\"a}ki and Anne Tj{\o}nneland and Uitterlinden, \{Andr{\'e} G.\} and Fernando Rivadeneira and Franco, \{Oscar H.\} and German, \{J. Bruce\} and Siscovick, \{David S.\} and Cupples, \{L. Adrienne\} and Ordov{\'a}s, \{Jos{\'e} M.\}",

note = "Publisher Copyright: {\textcopyright} 2017 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim",

year = "2018",

month = feb,

day = "1",

doi = "10.1002/mnfr.201700347",

language = "English",

volume = "62",

number = "3",

}

Smith, CE, Follis, JL, Dashti, HS, Tanaka, T, Graff, M, Fretts, AM, Kilpeläinen, TO, Wojczynski, MK, Richardson, K, Nalls, MA, Schulz, CA, Liu, Y, Frazier-Wood, AC, van Eekelen, E, Wang, C, de Vries, PS, Mikkilä, V, Rohde, R, Psaty, BM, Hansen, T, Feitosa, MF, Lai, CQ, Houston, DK, Ferruci, L, Ericson, U, Wang, Z, de Mutsert, R, Oddy, WH, de Jonge, EAL, Seppälä, I, Justice, AE, Lemaitre, RN, Sørensen, TIA, Province, MA, Parnell, LD, Garcia, ME, Bandinelli, S, Orho-Melander, M, Rich, SS, Rosendaal, FR, Pennell, CE, Kiefte-de Jong, JC, Kähönen, M, Young, KL, Pedersen, O, Aslibekyan, S, Rotter, JI, Mook-Kanamori, DO, Zillikens, MC, Raitakari, OT, North, KE, Overvad, K, Arnett, DK, Hofman, A, Lehtimäki, T, Tjønneland, A, Uitterlinden, AG, Rivadeneira, F, Franco, OH, German, JB, Siscovick, DS, Cupples, LA & Ordovás, JM 2018, 'Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent', Molecular Nutrition and Food Research, vol. 62, no. 3, 1700347. https://doi.org/10.1002/mnfr.201700347

TY - JOUR

T1 - Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

AU - Smith, Caren E.

AU - Follis, Jack L.

AU - Dashti, Hassan S.

AU - Tanaka, Toshiko

AU - Graff, Mariaelisa

AU - Fretts, Amanda M.

AU - Kilpeläinen, Tuomas O.

AU - Wojczynski, Mary K.

AU - Richardson, Kris

AU - Nalls, Mike A.

AU - Schulz, Christina Alexandra

AU - Liu, Yongmei

AU - Frazier-Wood, Alexis C.

AU - van Eekelen, Esther

AU - Wang, Carol

AU - de Vries, Paul S.

AU - Mikkilä, Vera

AU - Rohde, Rebecca

AU - Psaty, Bruce M.

AU - Hansen, Torben

AU - Feitosa, Mary F.

AU - Lai, Chao Qiang

AU - Houston, Denise K.

AU - Ferruci, Luigi

AU - Ericson, Ulrika

AU - Wang, Zhe

AU - de Mutsert, Renée

AU - Oddy, Wendy H.

AU - de Jonge, Ester A.L.

AU - Seppälä, Ilkka

AU - Justice, Anne E.

AU - Lemaitre, Rozenn N.

AU - Sørensen, Thorkild I.A.

AU - Province, Michael A.

AU - Parnell, Laurence D.

AU - Garcia, Melissa E.

AU - Bandinelli, Stefania

AU - Orho-Melander, Marju

AU - Rich, Stephen S.

AU - Rosendaal, Frits R.

AU - Pennell, Craig E.

AU - Kiefte-de Jong, Jessica C.

AU - Kähönen, Mika

AU - Young, Kristin L.

AU - Pedersen, Oluf

AU - Aslibekyan, Stella

AU - Rotter, Jerome I.

AU - Mook-Kanamori, Dennis O.

AU - Zillikens, M. Carola

AU - Raitakari, Olli T.

AU - North, Kari E.

AU - Overvad, Kim

AU - Arnett, Donna K.

AU - Hofman, Albert

AU - Lehtimäki, Terho

AU - Tjønneland, Anne

AU - Uitterlinden, André G.

AU - Rivadeneira, Fernando

AU - Franco, Oscar H.

AU - German, J. Bruce

AU - Siscovick, David S.

AU - Cupples, L. Adrienne

AU - Ordovás, José M.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - CHARGE consortium

KW - body mass index

KW - dairy intake

KW - genome-wide interaction study

KW - meta-analysis

UR - https://www.scopus.com/pages/publications/85041378879

UR - https://www.scopus.com/inward/citedby.url?scp=85041378879&partnerID=8YFLogxK

U2 - 10.1002/mnfr.201700347

DO - 10.1002/mnfr.201700347

M3 - Article

C2 - 28941034

AN - SCOPUS:85041378879

SN - 1613-4125

VL - 62

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

IS - 3

M1 - 1700347

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this