Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study
MetadataShow full item record
Cambridge University Press
Vissers, L... [et al.] (2021). Milk intake and incident stroke and CHD in populations of European descent: A Mendelian randomisation study. British Journal of Nutrition, 1-9. doi:[10.1017/S0007114521004244]
SponsorshipNetherlands Heart Foundation 2015T019; UK Research & Innovation (UKRI) Medical Research Council UK (MRC); European Commission MC_UU_12015/5; NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014; European Commission LSHM_CT_2006_037197; Cancer Research UK C8221/A19170; European Commission European Commission Joint Research Centre; International Agency for Research on Cancer; Danish Cancer Society; Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany); Federal Ministry of Education & Research (BMBF); Deutsche Krebshilfe Deutsches Krebsforschungszentrum (Germany); Federal Ministry of Education & Research (BMBF); Fondazione AIRC per la ricerca sul cancro Consiglio Nazionale delle Ricerche (CNR); Netherlands Government Netherlands Government; World Cancer Research Fund International (WCRF); Netherlands Government; Instituto de Salud Carlos III PI13/00061 PI13/01162; Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain); ISCIII Health Research Funds (FEDER funds/European Regional Development Fund ERDF) (Spain) RD12/0036/0018; Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden); European Commission Framework Programme 7 HEALTH-F2-2012-279233 European Research Council (ERC) European Commission 268834; UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/L003120/1 British Heart Foundation RG13/13/30194 RG/18/13/33946 National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust) UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1 Cancer Research UK C8221/A19170 14136 C570/A16491
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 (beta = 13 center dot 7 g/d; 95 % CI 8 center dot 4, 19 center dot 1) and EPIC-NL (36 center dot 8 g/d; 95 % CI 20 center dot 0, 53 center dot 5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1 center dot 05; 95 % CI 0 center dot 94, 1 center dot 16) or CHD (1 center dot 02; 95 % CI 0 center dot 96, 1 center dot 08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1 center dot 02; 95 % CI 0 center dot 99, 1 center dot 05) or CHD (OR 0 center dot 99; 95 % CI 0 center dot 95, 1 center dot 03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.