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Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Sluijs, I 
Burgess, S 
Forouhi, NG 

Abstract

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Description

Keywords

CHD, Dairy, Mendelian randomisation, Milk, Stroke, Humans, Adult, Animals, Milk, Prospective Studies, Risk Factors, Cardiovascular Diseases, Stroke, Neoplasms, European People

Journal Title

Br J Nutr

Conference Name

Journal ISSN

0007-1145
1475-2662

Volume Title

Publisher

Cambridge University Press (CUP)
Sponsorship
MRC (MC_UU_00006/1)
MRC (MC_UU_00006/3)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Department of Health (via National Institute for Health Research (NIHR)) (NIHR202397)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MC_UU_00002/7)
Medical Research Council (MC_UU_12015/5)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (CH/12/2/29428)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (G1000143)
European Research Council (268834)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)