Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region: an individual-based pooled analysis of 40 twin cohorts

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ABSTRACT

Background

Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.

Objective

We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.

Design

We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).

Results

The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20–29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70–79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20–29 to 60–69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.

Conclusions

The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.

Key Words

BMI
adults
genetics
twins
international comparisons

Abbreviations

CODATwins
Collaborative Project of Development of Anthropometrical Measures in Twins
GWA
genome-wide association
OSDZ
opposite-sex dizygotic
SSDZ
same-sex dizygotic

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The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, National Institute of Mental Health, Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institute on Aging, or US Department of Veterans Affairs.

Supported by Academy of Finland grant 266592 (this study was conducted within the CODATwins project). Collaborating projects were supported as follows: The Australian Twin Registry is supported by National Health and Medical Research Council Centre of Research Excellence grant 1079102 administered by the University of Melbourne. The California Twin Program was supported by NIH grant 1R01ESO15150-01 and California Tobacco-Related Disease Research Program grants 7RT-0134H, 8RT-0107H, and 6RT-0354H. The Carolina African American Twin Study of Aging was funded by National Institute on Aging grant 1R01-AG13662-01A2 to KEW. The Colorado Twin Registry is funded by National Institute on Drug Abuse–funded center grant DA011015 and Longitudinal Twin Study grant HD10333. BMH is supported by NIH grant 5T32DA017637-11. The Danish Twin Registry is supported by NIH grant P01AG08761 and by the National Program for Research Infrastructure 2007 from the Velux Foundation, the Research Council for Health and Disease, and the Danish Agency for Science, Technology, and Innovation. Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins (a Belgian nonprofit association for scientific research in multiple births). Data collection and analysis in Finnish twin cohorts was supported by European Network for Genetic and Genomic Epidemiology FP7-HEALTH-F4-2007 grant 201413; National Institute of Alcohol Abuse and Alcoholism grants AA12502, AA00145, and AA09203; Academy of Finland Center of Excellence in Complex Disease Genetics grants 213506 and 129680; and Academy of Finland grants 100499, 205585, 118555, 141054, 265240, 263278, and 264146 to JK. KHP is supported by Academy of Finland grant 266286; Academy of Finland Centre of Excellence in Research on Mitochondria, Metabolism, and Disease grant 272376; and the Novo Nordisk Foundation, Jalmari and Rauha Ahokas Foundation, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, and Helsinki University Central Hospital. KS is supported by Osaka University’s International Joint Research Promotion Program. Waves 1–3 of Genesis 12–19 were funded by the William T Grant Foundation, the University of London Central Research fund, and Medical Research Council Training Fellowship G81/343 and Career Development Award G120/635 to TCE. Wave 4 was supported by Economic and Social Research Council grant RES-000-22-2206 and Institute of Social Psychiatry grant 06/07–11 to AMG, who was also supported at that time by Leverhulme Research Fellowship RF/2/RFG/2008/0145. Wave 5 was supported by funding from Goldsmiths, University of London to AMG. Anthropometric measurements of the Hungarian twins were supported by MedExpert Ltd. The Korean Twin-Family Register was supported by Global Research Network Program of the National Research Foundation grant NRF 2011-220-E00006. The Michigan State University Twin Registry has been supported by Michigan State University and National Institute of Mental Health grants R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, and R03MH63851-01; grant R01HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development; and grant 11-SPG-2518 from the Michigan State University Foundation. The Murcia Twin Registry is supported by Fundación Séneca, Spanish Ministry of Science and Innovation grants PSI2009-11560 and PSI2014-56680-R, and Regional Agency for Science and Technology grants 08633/PHCS/08, 15302/PHCS/10, and 19479/PI/14. Data collection and research stemming from the Norwegian Twin Registry is supported in part by European Union Seventh Framework Programme European Network for Genetic and Genomic Epidemiology Consortium grant HEALTH-F4-2007-201413 and Biobank Standardisation and Harmonisation for Research Excellence in the European Union grant HEALTH-F4-2010-261433. The National Academy of Sciences–National Research Council Twin Registry is supported by NIH grant R21AG039572. The Netherlands Twin Register is supported by the Avera Institute, VU University Institute for Health and Care Research, European Research Council grant 230374, and Netherlands Organization for Scientific Research and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, and Spinozapremie 56-464-14192. The South Korea Twin Registry is supported by National Research Foundation of Korea grant NRF-371-2011-1 B00047. SYÖ and FA are supported by Kırıkkale University Research grant KKU 2009/43 and The Scientific and Techological Research Council of Turkey grant 114C117. TwinsUK is funded by the Medical Research Council, the European Union, the National Institute for Health Research–funded BioResource, and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ National Health Service Foundation Trust in partnership with King’s College London. The University of Southern California Twin Study is funded by National Institute of Mental Health grant R01 MH58354. The Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by NIH grant RC2HL103416 (to DB, principal investigator). The Vietnam Era Twin Study of Aging was supported by NIH National Institute on Aging grants R01AG018384, R01AG018386, R01AG022381, and R01AG022982 and in part by resources from the US Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the US Department of Veterans Affairs Office of Research and Development provided financial support for the development and maintenance of the Vietnam Era Twin Registry. The West Japan Twins and Higher Order Multiple Births Registry was supported by grant-in-aid for scientific research (B) 15H05105 from the Japan Society for the Promotion of Science.