Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study-Reference-Cited by-同舟云学术

Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study

Published:2023-06-09 Issue:5 Volume:52 Page:1579-1591
ISSN:0300-5771
Container-title:International Journal of Epidemiology
language:en
Short-container-title:

Author:

Howe Laurence J¹²^ORCID,Rasheed Humaira¹³⁴,Jones Paul R⁵,Boomsma Dorret I⁶⁷^ORCID,Evans David M¹⁸⁹^ORCID,Giannelis Alexandros¹⁰,Hayward Caroline¹¹^ORCID,Hopper John L¹²,Hughes Amanda¹²,Lahtinen Hannu¹³^ORCID,Li Shuai¹²¹⁴¹⁵^ORCID,Lind Penelope A¹⁶¹⁷¹⁸,Martin Nicholas G¹⁹,Martikainen Pekka¹³²⁰²¹^ORCID,Medland Sarah E¹⁶¹⁸²²,Morris Tim T¹²^ORCID,Nivard Michel G⁶,Pingault Jean-Baptiste²³²⁴,Silventoinen Karri¹³,Smith Jennifer A²⁵²⁶^ORCID,Willoughby Emily A¹⁰,Wilson James F¹¹²⁷,Ahlskog Rafael,Andreassen Ole A,Ask Helga,Campbell Archie,Cheesman Rosa,Cho Yoonsu,Christensen Kaare,Corfield Elizabeth C,Dahm Christina C,Havdahl Alexandra,Hill William D,Kerr Shona M,Latvala Antti,Nygaard Marianne,Palviainen Teemu,Pedersen Nancy L,Plomin Robert,Southey Melissa C,Stoltenberg Camilla,Åsvold Bjørn Olav³²⁸^ORCID,Næss Øyvind E⁵²⁹,Davey Smith George¹²^ORCID,Kaprio Jaakko³⁰,Brumpton Ben¹³^ORCID,Davies Neil M¹³³¹³²^ORCID,

Affiliation:

1. Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol , UK

2. Population Health Sciences, Bristol Medical School, University of Bristol , Bristol, UK

3. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology , Trondheim, Norway

4. Department of Medicine and Laboratory Sciences, University of Oslo , Oslo, Norway

5. Department of Community Medicine and Global Health, Institute of Health and Society, Faculty of Medicine, University of Oslo , Oslo, Norway

6. Department of Biological Psychology, Netherlands Twin Registry, Vrije Universiteit , Amsterdam, Netherlands

7. Amsterdam Public Health (APH) and Amsterdam Reproduction and Development (AR&D)

8. University of Queensland Diamantina Institute, University of Queensland , Brisbane, Australia

9. Institute for Molecular Bioscience, University of Queensland , Brisbane, Australia

10. Department of Psychology, University of Minnesota , Minneapolis, MN, USA

11. MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital , Edinburgh, UK

12. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne , Parkville, Victoria, Australia

13. Population Research Unit, University of Helsinki , Helsinki, Finland

14. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK

15. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University , Clayton, Victoria, Australia

16. Psychiatric Genetics, QIMR Berghofer Medical Research Institute , Brisbane, Australia

17. School of Biomedical Sciences, Queensland University of Technology , Brisbane, Australia

18. Faculty of Medicine, University of Queensland , Brisbane, Australia

19. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia

20. The Max Planck Institute for Demographic Research , Germany

21. Department of Public Health Sciences, Stockholm University , Sweden

22. School of Psychology, University of Queensland , Brisbane, Australia

23. Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, UK

24. Department of Clinical, Educational and Health Psychology, University College London , London, UK

25. Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, MI, USA

26. Survey Research Center, Institute for Social Research, University of Michigan , Ann Arbor, MI, USA

27. Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place , Edinburgh, UK

28. Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital , Trondheim, Norway

29. Norwegian Institute of Public Health , Oslo, Norway

30. Institute for Molecular Medicine FIMM, University of Helsinki , Helsinki, Finland

31. Division of Psychiatry, University College London , London, UK

32. Department of Statistical Sciences, University College London , London, UK

Abstract

Abstract Background Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Methods Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Results Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant–outcome associations attenuated in the within-sibship model, but genetic variant–educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. Conclusions These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

Funder

University of Bristol

MRC Integrative Epidemiology Unit

Trøndelag Health Study

Faculty of Medicine and Health Sciences

Norwegian University of Science and Technology

Trøndelag County Council, Central Norway Regional Health Authority

Norwegian Institute of Public Health

National Institutes of Health

University of Michigan

Research Council of Norway

Liaison Committee for Education, Research and Innovation in Central Norway