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Epidemiology and Population Health

The role of family factors in the association between early adulthood BMI and risk of cardiovascular disease. An intergenerational study of BMI in early adulthood and cardiovascular mortality in parents, aunts and uncles

Abstract

Background

High body mass index (BMI) in childhood and adolescence is related to cardiovascular disease (CVD). Causality is not established because common genetic or early life socioeconomic factors (family factors) may explain this relationship. We aimed to study the role of family factors in the association between BMI and CVD by investigating if early adulthood BMI in conscripts and CVD mortality in their parents/aunts/uncles are related.

Methods

Data from the Armed Forces Personnel Database (including height and weight among conscripts) were linked with data from the Norwegian Population Registry, generational data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry using unique personal identification numbers. The study sample (N = 369,464) was Norwegian males born 1967–1993, who could be linked to both parents and at least one maternal and one paternal aunt or uncle. Subsamples were identified as conscripts whose parents/aunts/uncles had data on cardiovascular risk factors available from Norwegian health surveys. Cox proportional hazards regression models were used to estimate hazard ratios (HR) of CVD mortality in the parental generation according to BMI categories of conscripts.

Results

Parents of conscripts with obesity or overweight had a higher hazard of CVD death (fathers HR obese: 1.99 (1.79, 2.21), overweight: 1.33 (1.24, 1.42) mothers HR obese: 1.65 (1.32, 2.07), overweight: 1.23 (1.07, 1.42)) than parents of normal- or underweight conscripts. Aunts and uncles of conscripts with obesity and overweight had an elevated hazard of CVD death, but less so than parents. Adjustment for CVD risk factors attenuated the results in parents, aunts and uncles.

Conclusions

Family factors may impact the relationship between early adulthood overweight and CVD in parents. These can be genes with impact on BMI over generations and genes with a pleiotropic effect on both obesity and CVD, as well as shared environment over generations.

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Fig. 1: Flow chart.

Data availability

Data are owned by Norwegian Institute of Public Health (NIPH) and cannot be shared. Application has to be sent to NIPH after approval of study from Norwegian Regional Committees for Medical and Health Research Ethics

References

  1. 1.

    Umer A, Kelley GA, Cottrell LE, Giacobbi P, Innes KE, Lilly CL. Childhood obesity and adult cardiovascular disease risk factors: a systematic review with meta-analyses. BMC Public Health. 2017;17:683.

    Article  Google Scholar 

  2. 2.

    Kjøllesdal M, Ariansen I, Næss Ø. Early adulthood weight, subsequent midlife weight change and risk of cardiovascular disease mortality: an analysis of Norwegian cardiovascular surveys. Int J Obes. 2020;44:399–408.

    Article  Google Scholar 

  3. 3.

    Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and risk of the adult metabolic syndrome: a systematic review. Int J Obes (Lond). 2012;36:1–11.

    CAS  Article  Google Scholar 

  4. 4.

    de Mestral C, Stringhini S. Socioeconomic status and cardiovascular disease: an update. Curr Cardiol Rep. 2017;19:115.

    Article  Google Scholar 

  5. 5.

    McLaren L. Socioeconomic status and obesity. Epidemiol Rev. 2007;29:29–48.

    Article  Google Scholar 

  6. 6.

    Newton S, Braithwaite D, Akinyemiju TF. Socio-economic status over the life course and obesity: systematic review and meta-analysis. PLoS One. 2017;12:e0177151.

    Article  Google Scholar 

  7. 7.

    Loos RJ. The genetics of adiposity. Curr Opin Genet Dev. 2018;50:86–95.

    CAS  Article  Google Scholar 

  8. 8.

    Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G. Use of genetic variation to separate the effects of early and later life adiposity on disease risk: Mendelian randomisation study. BMJ. 2020;369:m1203 https://doi.org/10.1136/bmj.m1203.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dhana K, Haines J, Liu G, Zhang C, Wang X, Field AE, et al. Association between maternal adherence to healthy lifestyle practices and risk of obesity in offspring: results from two prospective cohort studies of mother-child pairs in the United States. BMJ. 2018;362:k2486 https://doi.org/10.1136/bmj.k2486.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Næss M, Sund E, Holmen TL, Kvaløy K. Implications of parental lifestyle changes and education level on adolescent offspring weight: a population based cohort study—The HUNT Study, Norway. BMJ Open. 2018;8:e023406 https://doi.org/10.1136/bmjopen-2018-023406.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Davey Smith G, Hypponen E, Power C, Lawlor DA. Offspring birthweight and parentsal mortality: prospective observational study and meta-analysis. Am J Epidemiol. 2007;166:160–9.

    Article  Google Scholar 

  12. 12.

    Carreras-Torres R, Johansson M, Haycock PC, Relton CL, Davey Smith G, Brennan P, et al. Role of obesity in smoking behaviour: Mendelian randomization study in UK Biobank. BMJ. 2018;361:k1767.

    Article  Google Scholar 

  13. 13.

    Paajanen TA, Oksala NK, Kuukasjarvi P, Karhunen PJ. Short stature is associated with coronary heart disease: a systematic review of the literature and a meta-analysis. Eur Heart J. 2010;31:1802–9.

    Article  Google Scholar 

  14. 14.

    Nelson CP, Hamby SE, Saleheen D, Hopewell JC, Zeng L, Assimes TL, et al. Genetically determined height and coronary artery disease. N Engl J Med. 2015;372:1608–18.

    CAS  Article  Google Scholar 

  15. 15.

    Collaboration TERF. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis. Int J Epidemiol. 2012;41:1419–33.

    Article  Google Scholar 

  16. 16.

    Bjartveit K, Foss OP, Gjervig T, Lund-Larsen PG. The cardiovascular disease study in Norwegian counties. Background and organization. Acta Med Scand Suppl. 1979;634:1–70.

    CAS  PubMed  Google Scholar 

  17. 17.

    Tverdal A, Hjellvik V, Selmer R. Heart rate and mortality from cardiovascular causes: a 12 year follow-up study of 379,843 men and women aged 40-45 years. Eur Heart J. 2008;29:2772–81.

    Article  Google Scholar 

  18. 18.

    Naess O, Sogaard AJ, Arnesen E, Beckstrom AC, Bjertness E, Engeland A, et al. Cohort profile: cohort of Norway (CONOR). Int J Epidemiol. 2008;37:481–5.

    Article  Google Scholar 

  19. 19.

    Graff-Iversen S. External female hormones, serum lipids and mortality—Population studies of Norwegian women. Oslo, Norway: University of Oslo; 2005.

  20. 20.

    Thelle DS, Selmer R, Gjesdal K, Sakshaug S, Jugessur A, Graff-Iversen S, et al. Resting heart rate and physical activity as risk factors for lone atrial fibrillation: a prospective study of 309,540 men and women. Heart. 2013;99:1755–60.

    Article  Google Scholar 

  21. 21.

    Foss OP, Urdal P. Cholesterol for more than 25 years: could the results be compared throughout all this time? Norsk Epidemiologi. 2003;13:85–8.

    Google Scholar 

  22. 22.

    Davey Smith G. Assessing Intrauterine Influences on Offspring Health Outcomes: Can Epidemiological Studies Yield Robust Findings? Basic Clin Pharmacol Toxicol. 2007;102:245–56.

    Article  Google Scholar 

  23. 23.

    Shaikh F, Kjøllesdal M, Carslake D, Thoresen M, Næss Ø. Cardiovascular risk factors in extended family members and birthweight in offspring. J Dev Orig Health Dis. 2021;11:1–7. https://doi.org/10.1017/S2040174421000076.

  24. 24.

    Shaikh F, Kjøllesdal MK, Carslake D, Stoltenberg C, Davey Smith G, Næss Ø. Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births. Int J Epidemiol. 2019. https://doi.org/10.1093/ije/dyz156.

  25. 25.

    Kong A, Thorleifsson G, Frigge ML, Vilhjalmsson BJ, Young AI, Thorgeirsson TE, et al. The nature of nurture. Effects of parental genotypes. Science. 2018;359:424–8.

    CAS  Article  Google Scholar 

  26. 26.

    Brumpton B, Sanderson E, Heilbron K, Hartwig FP, Harrison S, Vie GÅ, et al. Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Nat Commun. 2020;14:3325.

    Google Scholar 

  27. 27.

    Fleten C, Nystad W, Stigum H, Skjaerven R, Lawlor DA, Davey Smith G, et al. Parent-offspring body mass index associations in the Norwegian Mother and Child Cohort Study: a family-based approach to studying the role of the intrauterine environment in childhood adiposity. Am J Epidemiol. 2012;176:83–92.

    Article  Google Scholar 

  28. 28.

    Davey Smith G, Sterne JA, Fraser A, Tynelius P, Lawlor DA, Rasmussen F. The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study. BMJ. 2009;39:b5043 https://doi.org/10.1136/bmj.b5043.

    Article  Google Scholar 

  29. 29.

    Vik KL, Romundstad P, Carslake D, Davey Smith G, Nilsen T. Comparison of father-offspring and mother-offspring associations of cardiovascular risk factors: family linkage within the population-based HUNT study, Norway. Int J Epidemiol. 2014;43:760–71.

    Article  Google Scholar 

  30. 30.

    Knuiman MW, Divitini ML, Welborn TA, Bartholomew HC. Familial correlations, cohabitation effects, and heritability for cardiovascular risk factors. Ann Epidemiol. 1996;6:188–94.

    CAS  Article  Google Scholar 

  31. 31.

    Hu Y, He L, Wu Y, Ma G, Li L, Hu Y. Familial correlation and aggregation of body mass index and blood pressure in Chinese Han population. BMC Public Health. 2013;13:686.

    Article  Google Scholar 

  32. 32.

    Norwegian Institute of Public Health. Public Health report. Overweight and Obesity in Norway. https://www.fhi.no/en/op/hin/health-disease/overweight-and-obesity-in-norway-/. Assessed 25-08.2021.

Download references

Funding

This work was supported by the Norwegian research Council [grant number 213788]. GDS and DC works in a unit which receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1).

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Contributions

ØN and MK conceived the idea of the article, MK did the statistical analyses and drafted the article and all authors have critically revised the manuscript and contributed in the final stage of writing.

Corresponding author

Correspondence to M. K. R. Kjøllesdal.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by the Norwegian Regional Committees for Medical and Health Research Ethics (REK) (2012/827). Written informed consent was obtained from participants in the Age 40 Program and CONOR. Participants in the Counties studies gave written permission for their results to be sent to their physician. Permission to be absolved from this professional secrecy has been granted and concession to handle this personal health information has been given by the authorities. The health studies have been conducted in full accordance with the World Medical Association Declaration of Helsinki.

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Kjøllesdal, M.K.R., Carslake, D., Smith, G.D. et al. The role of family factors in the association between early adulthood BMI and risk of cardiovascular disease. An intergenerational study of BMI in early adulthood and cardiovascular mortality in parents, aunts and uncles. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00987-z

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