Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

Mendelian Randomization of Dairy Consumption Working Group; Peter Eastwood

doi:10.1373/clinchem.2017.280701

Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

Mendelian Randomization of Dairy Consumption Working Group, Peter Eastwood

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Abstract

BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m² per serving/day; 95% CI, 0.00- 0.06; P=0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P=3.15 x 10¹²) and 0.12 (95% CI, 0.06-0.17) kg/m² higher BMI (P = 2.11 x 10⁵,). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m² per serving/day; 95% CI, 0.27- 0.92; P = 3.0 x 10⁴). CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

Original language	English
Pages (from-to)	183-191
Number of pages	9
Journal	Clinical Chemistry
Volume	64
Issue number	1
DOIs	https://doi.org/10.1373/clinchem.2017.280701
Publication status	Published - Jan 2018
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments: The authors thank the staff and participants of the ARIC study for their important contributions. The authors thank the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The authors also acknowledge the funding agencies supporting the Northern Sweden Diet Database and the Västerbotten Intervention Project, including the Swedish Research Council. The authors thank Ville Aalto, Irina Lisi-nen, and Mika Helminen for their expert technical assistance in the statistical analyses. The PREDIMED-Valencia study also acknowledges the collaborative support provided by the Real Colegio Complutense at Harvard University. The authors thank the Raine Study participants and their families, as well as the Raine Study research staff for cohort coordination and data collection. The authors thank the NH&MRC for their long-term funding to the study during the past 25 years and also the following institutes for providing funding for Core Management of the Raine Study: The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Telethon Kids Institute, the Women’s and Infants’ Research Foundation (King Edward Memorial Hospital), and Edith Cowan University. The authors thank the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility)

Publisher Copyright:
© 2017 American Association for Clinical Chemistry.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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@article{7ee33960489a4290a6883a154865278f,

title = "Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies",

abstract = "BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00- 0.06; P=0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P=3.15 x 1012) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher BMI (P = 2.11 x 105,). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27- 0.92; P = 3.0 x 104). CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.",

author = "{Mendelian Randomization of Dairy Consumption Working Group} and Tao Huang and Ming Ding and Bergholdt, {Helle K.M.} and Tiange Wang and Yoriko Heianza and Dian-jianyi Sun and Frazier-Wood, {Alexis C.} and Stella Aslibekyan and North, {Kari E.} and Trudy Voortman and Mariaelisa Graff and Smith, {Caren E.} and Chao-Qiang Lai and Anette Varbo and Lemaitre, {Rozenn N.} and {de Jonge}, {M. Ester A.L.} and Frederic Fumeron and Dolores Corella and Wang, {Carol A.} and Anne Tj{\o}nneland and Kim Overvad and S{\o}rensen, {Thorkild I A} and Feitosa, {Mary F.} and Wojczynski, {Mary K.} and Mika K{\"a}h{\"o}nen and Frida Renstr{\"o}m and Psaty, {Bruce M.} and David Siscovick and In{\^e}s Barroso and Ingegerd Johansson and Dena Hernandez and Luigi Ferrucci and Stefania Bandinelli and Allan Linneberg and Zillikens, {M. Carola} and Sandholt, {Camilla Helene} and Oluf Pedersen and Torben Hansen and Christina-Alexandra Schulz and Emily Sonestedt and Marju Orho-Melander and Tzu-An Chen and Rotter, {Jerome I.} and Allison, {Mathew A.} and Rich, {Stephen S} and Sorl{\'i}, {Jose V.} and Oscar Coltell and Pennell, {Craig E.} and Peter Eastwood and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and {Van Rooij}, {Frank J.A.} and Chu, {Audrey Y.} and Rose, {Lynda M.} and Ridker, {Paul M.} and Jorma Viikari and Olli Raitakari and Terho Lehtim{\"a}ki and Vera Mikkil{\"a}¨ and Willett, {Walter C.} and Yujie Wang and Tucker, {Katherine L.} and Ordovas, {Jose M.} and Kilpel{\"a}inen, {Tuomas O.} and Province, {Michael A.} and Franks, {Paul W.} and Arnett, {Donna K.} and Toshiko Tanaka and Ulla Toft and Ulrika Ericson and Franco, {Oscar H.} and Dariush Mozaffarian and Frank Hu and Chasman, {Daniel I.} and Nordestgaard, {B{\o}rge G.} and Christina Ellervik",

note = "Funding Information: Acknowledgments: The authors thank the staff and participants of the ARIC study for their important contributions. The authors thank the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The authors also acknowledge the funding agencies supporting the Northern Sweden Diet Database and the V{\"a}sterbotten Intervention Project, including the Swedish Research Council. The authors thank Ville Aalto, Irina Lisi-nen, and Mika Helminen for their expert technical assistance in the statistical analyses. The PREDIMED-Valencia study also acknowledges the collaborative support provided by the Real Colegio Complutense at Harvard University. The authors thank the Raine Study participants and their families, as well as the Raine Study research staff for cohort coordination and data collection. The authors thank the NH&MRC for their long-term funding to the study during the past 25 years and also the following institutes for providing funding for Core Management of the Raine Study: The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Telethon Kids Institute, the Women{\textquoteright}s and Infants{\textquoteright} Research Foundation (King Edward Memorial Hospital), and Edith Cowan University. The authors thank the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility) Publisher Copyright: {\textcopyright} 2017 American Association for Clinical Chemistry. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2018",

month = jan,

doi = "10.1373/clinchem.2017.280701",

language = "English",

volume = "64",

pages = "183--191",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "AMER ASSOC CLINICAL CHEMISTRY",

number = "1",

}

TY - JOUR

T1 - Dairy consumption and body mass index among adults

T2 - Mendelian randomization analysis of 184802 individuals from 25 studies

AU - Mendelian Randomization of Dairy Consumption Working Group

AU - Huang, Tao

AU - Ding, Ming

AU - Bergholdt, Helle K.M.

AU - Wang, Tiange

AU - Heianza, Yoriko

AU - Sun, Dian-jianyi

AU - Frazier-Wood, Alexis C.

AU - Aslibekyan, Stella

AU - North, Kari E.

AU - Voortman, Trudy

AU - Graff, Mariaelisa

AU - Smith, Caren E.

AU - Lai, Chao-Qiang

AU - Varbo, Anette

AU - Lemaitre, Rozenn N.

AU - de Jonge, M. Ester A.L.

AU - Fumeron, Frederic

AU - Corella, Dolores

AU - Wang, Carol A.

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Sørensen, Thorkild I A

AU - Feitosa, Mary F.

AU - Wojczynski, Mary K.

AU - Kähönen, Mika

AU - Renström, Frida

AU - Psaty, Bruce M.

AU - Siscovick, David

AU - Barroso, Inês

AU - Johansson, Ingegerd

AU - Hernandez, Dena

AU - Ferrucci, Luigi

AU - Bandinelli, Stefania

AU - Linneberg, Allan

AU - Zillikens, M. Carola

AU - Sandholt, Camilla Helene

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Schulz, Christina-Alexandra

AU - Sonestedt, Emily

AU - Orho-Melander, Marju

AU - Chen, Tzu-An

AU - Rotter, Jerome I.

AU - Allison, Mathew A.

AU - Rich, Stephen S

AU - Sorlí, Jose V.

AU - Coltell, Oscar

AU - Pennell, Craig E.

AU - Eastwood, Peter

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Van Rooij, Frank J.A.

AU - Chu, Audrey Y.

AU - Rose, Lynda M.

AU - Ridker, Paul M.

AU - Viikari, Jorma

AU - Raitakari, Olli

AU - Lehtimäki, Terho

AU - Mikkilä¨, Vera

AU - Willett, Walter C.

AU - Wang, Yujie

AU - Tucker, Katherine L.

AU - Ordovas, Jose M.

AU - Kilpeläinen, Tuomas O.

AU - Province, Michael A.

AU - Franks, Paul W.

AU - Arnett, Donna K.

AU - Tanaka, Toshiko

AU - Toft, Ulla

AU - Ericson, Ulrika

AU - Franco, Oscar H.

AU - Mozaffarian, Dariush

AU - Hu, Frank

AU - Chasman, Daniel I.

AU - Nordestgaard, Børge G.

AU - Ellervik, Christina

N1 - Funding Information: Acknowledgments: The authors thank the staff and participants of the ARIC study for their important contributions. The authors thank the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The authors also acknowledge the funding agencies supporting the Northern Sweden Diet Database and the Västerbotten Intervention Project, including the Swedish Research Council. The authors thank Ville Aalto, Irina Lisi-nen, and Mika Helminen for their expert technical assistance in the statistical analyses. The PREDIMED-Valencia study also acknowledges the collaborative support provided by the Real Colegio Complutense at Harvard University. The authors thank the Raine Study participants and their families, as well as the Raine Study research staff for cohort coordination and data collection. The authors thank the NH&MRC for their long-term funding to the study during the past 25 years and also the following institutes for providing funding for Core Management of the Raine Study: The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Telethon Kids Institute, the Women’s and Infants’ Research Foundation (King Edward Memorial Hospital), and Edith Cowan University. The authors thank the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility) Publisher Copyright: © 2017 American Association for Clinical Chemistry. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/1

Y1 - 2018/1

N2 - BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00- 0.06; P=0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P=3.15 x 1012) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher BMI (P = 2.11 x 105,). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27- 0.92; P = 3.0 x 104). CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

AB - BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00- 0.06; P=0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P=3.15 x 1012) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher BMI (P = 2.11 x 105,). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27- 0.92; P = 3.0 x 104). CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

UR - http://www.scopus.com/inward/record.url?scp=85040031088&partnerID=8YFLogxK

U2 - 10.1373/clinchem.2017.280701

DO - 10.1373/clinchem.2017.280701

M3 - Article

C2 - 29187356

AN - SCOPUS:85040031088

SN - 0009-9147

VL - 64

SP - 183

EP - 191

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 1

ER -

Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

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