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

Karri Silventoinen^{1

2}, Aline Jelenkovic^{3

4}, Reijo Sund^{3

5}, Yoshie Yokoyama⁶, Yoon-Mi Hur⁷, Wendy Cozen^{8

9}, Amie E Hwang⁸, Thomas M Mack^{8

9}, Chika Honda², Fujio Inui^{2

10}, Yoshinori Iwatani², Mikio Watanabe², Rie Tomizawa², Kirsi H Pietiläinen^{11

12}, Aila Rissanen^{11

12}, Sisira H Siribaddana^{13

14}, Matthew Hotopf¹⁵, Athula Sumathipala^{13

16}, Fruhling Rijsdijk¹⁷, Qihua Tan¹⁸, Dongfeng Zhang¹⁹, Zengchang Pang²⁰, Maarit Piirtola^{3

21}, Sari Aaltonen^{3

22}, Sevgi Y Öncel²³, Fazil Aliev^{24

25

26}, Esther Rebato⁴, Jacob B Hjelmborg²⁷, Kaare Christensen^{27

28}, Axel Skytthe²⁷, Kirsten O Kyvik^{29

30}, Judy L Silberg³¹, Lindon J Eaves³¹, Tessa L Cutler³², Juan R Ordoñana^{33

34}, Juan F Sánchez-Romera^{33

34}, Lucia Colodro-Conde^{33

35}, Yun-Mi Song³⁶, Sarah Yang^{37

38}, Kayoung Lee³⁹, Carol E Franz⁴⁰, William S Kremen^{40

41}, Michael J Lyons⁴², Andreas Busjahn⁴³, Tracy L Nelson⁴⁴, Keith E Whitfield⁴⁵, Christian Kandler⁴⁶, Kerry L Jang⁴⁷, Margaret Gatz^{48

49}, David A Butler⁵⁰, Maria A Stazi⁵¹, Corrado Fagnani⁵¹, Cristina D'Ippolito⁵¹, Glen E Duncan⁵², Dedra Buchwald⁵², Nicholas G Martin⁵³, Sarah E Medland⁵³, Grant W Montgomery⁵⁴, Hoe-Uk Jeong⁷, Gary E Swan⁵⁵, Ruth Krasnow⁵⁶, Patrik Ke Magnusson⁴⁹, Nancy L Pedersen⁴⁹, Anna K Dahl Aslan^{49

57}, Tom A McAdams¹⁷, Thalia C Eley¹⁷, Alice M Gregory⁵⁸, Per Tynelius⁵⁹, Laura A Baker⁴⁸, Catherine Tuvblad^{48

60}, Gombojav Bayasgalan⁶¹, Danshiitsoodol Narandalai^{61

62}, Timothy D Spector⁶³, Massimo Mangino^{63

64}, Genevieve Lachance⁶³, S Alexandra Burt⁶⁵, Kelly L Klump⁶⁵, Jennifer R Harris⁶⁶, Ingunn Brandt⁶⁶, Thomas S Nilsen⁶⁶, Robert F Krueger⁶⁷, Matt McGue⁶⁷, Shandell Pahlen⁶⁷, Robin P Corley⁶⁸, Brooke M Huibregtse⁶⁸, Meike Bartels⁶⁹, Catharina Em van Beijsterveldt⁶⁹, Gonneke Willemsen⁶⁹, Jack H Goldberg⁷⁰, Finn Rasmussen⁵⁹, Adam D Tarnoki^{71

72}, David L Tarnoki^{71

72}, Catherine A Derom^{73

74}, Robert F Vlietinck⁷³, Ruth Jf Loos⁷⁵, John L Hopper^{37

32}, Joohon Sung^{37

38}, Hermine H Maes⁷⁶, Eric Turkheimer⁷⁷, Dorret I Boomsma⁶⁹, Thorkild Ia Sørensen^{78

79

80}, Jaakko Kaprio^{22

21}

Affiliations

¹ Departments of Social Research and karri.silventoinen@helsinki.fi.
² Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
³ Departments of Social Research and.
⁴ Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Leioa, Spain.
⁵ Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁶ Department of Public Health Nursing, Osaka City University, Osaka, Japan.
⁷ Department of Education, Mokpo National University, Jeonnam, South Korea.
⁸ Department of Preventive Medicine, Keck School of Medicine.
⁹ Norris Comprehensive Cancer Center, and.
¹⁰ Faculty of Health Science, Kio University, Nara, Japan.
¹¹ Obesity Research Unit, Research Programs Unit, University of Helsinki, Helsinki, Finland.
¹² Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
¹³ Institute of Research and Development, Battaramulla, Sri Lanka.
¹⁴ Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka.
¹⁵ National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust, Institute of Psychiatry Psychology and Neuroscience.
¹⁶ Research Institute for Primary Care and Health Sciences, School for Primary Care Research, Faculty of Health, Keele University, Staffordshire, United Kingdom.
¹⁷ Medical Research Council Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, and.
¹⁸ Unit of Epidemiology, Biostatistics, and Biodemography, Departments of Public Health and.
¹⁹ Department of Public Health, Qingdao University Medical College, Qingdao, China.
²⁰ Department of Noncommunicable Diseases Prevention, Qingdao Centers for Disease Control and Prevention, Qingdao, China.
²¹ Institute for Molecular Medicine, Helsinki, Finland.
²² Public Health, and.
²³ Department of Statistics, Faculty of Arts and Sciences, Kırıkkale University, Kırıkkale, Turkey.
²⁴ Faculty of Business, Karabuk University, Karabuk, Turkey.
²⁵ Departments of Psychology and.
²⁶ African American Studies.
²⁷ The Danish Twin Registry.
²⁸ Departments of Clinical Biochemistry and Pharmacology and Clinical Genetics, and.
²⁹ Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁰ Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
³¹ Department of Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, and.
³² The Australian Twin Registry, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia.
³³ Department of Human Anatomy and Psychobiology, University of Murcia, Murcia, Spain.
³⁴ Biomedical Research Institute of Murcia (IMIB)-Arrixaca, Murcia, Spain.
³⁵ Quantitative Genetics Laboratory and.
³⁶ Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³⁷ Department of Epidemiology, School of Public Health, and.
³⁸ Institute of Health and Environment, Seoul National University, Seoul, South Korea.
³⁹ Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
⁴⁰ Department of Psychiatry, University of California, San Diego, CA.
⁴¹ US Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health, La Jolla, CA.
⁴² Department of Psychology, Boston University, Boston, MA.
⁴³ HealthTwiSt GmbH, Berlin, Germany.
⁴⁴ Department of Health and Exercise Sciences, Colorado School of Public Health, Colorado State University, Aurora, CO.
⁴⁵ Psychology Department, Wayne State University, Detroit, MI.
⁴⁶ Department of Psychology, Bielefeld University, Bielefeld, Germany.
⁴⁷ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Departments of.
⁴⁸ Department of Psychology, University of Southern California, Los Angeles, CA.
⁴⁹ Medical Epidemiology and Biostatistics and.
⁵⁰ Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine, Washington, DC.
⁵¹ Italian National Institute of Health National Center for Epidemiology, Surveillance, and Health Promotion, Rome, Italy.
⁵² Washington State Twin Registry, Health Sciences, Washington State University, Spokane, WA.
⁵³ Genetic Epidemiology Department, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia.
⁵⁴ Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
⁵⁵ Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.
⁵⁶ Center for Health Sciences, SRI International, Menlo Park, CA.
⁵⁷ Institute of Gerontology and Aging Research Network, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
⁵⁸ Department of Psychology, Goldsmiths, University of London, London, United Kingdom.
⁵⁹ Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
⁶⁰ School of Law, Psychology, and Social Work, Örebro University, Örebro, Sweden.
⁶¹ Healthy Twin Association of Mongolia, Ulaanbaatar, Mongolia.
⁶² Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁶³ Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
⁶⁴ National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom.
⁶⁵ Michigan State University, East Lansing, Michigan.
⁶⁶ Norwegian Institute of Public Health, Oslo, Norway.
⁶⁷ Department of Psychology, University of Minnesota, Minneapolis, MN.
⁶⁸ Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.
⁶⁹ Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands.
⁷⁰ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
⁷¹ Department of Radiology, Semmelweis University, Budapest, Hungary.
⁷² Hungarian Twin Registry, Budapest, Hungary.
⁷³ Centre of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
⁷⁴ Department of Obstetrics and Gynaecology, Ghent University Hospitals, Ghent, Belgium.
⁷⁵ Charles Bronfman Institute for Personalized Medicine, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷⁶ Departments of Human and Molecular Genetics and Psychiatry, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA.
⁷⁷ Department of Psychology, University of Virginia, Charlottesville, VA.
⁷⁸ Section on Metabolic Genetics, Novo Nordisk Foundation Centre for Basic Metabolic Research, Copenhagen, Denmark.
⁷⁹ Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and.
⁸⁰ Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, Copenhagen, Denmark.

PMID: 28679550
PMCID: PMC5525120
DOI: 10.3945/ajcn.117.153643

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

Karri Silventoinen et al. Am J Clin Nutr. 2017 Aug.

. 2017 Aug;106(2):457-466.

doi: 10.3945/ajcn.117.153643. Epub 2017 Jul 5.

Authors

Affiliations

¹ Departments of Social Research and karri.silventoinen@helsinki.fi.
² Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
³ Departments of Social Research and.
⁴ Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Leioa, Spain.
⁵ Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁶ Department of Public Health Nursing, Osaka City University, Osaka, Japan.
⁷ Department of Education, Mokpo National University, Jeonnam, South Korea.
⁸ Department of Preventive Medicine, Keck School of Medicine.
⁹ Norris Comprehensive Cancer Center, and.
¹⁰ Faculty of Health Science, Kio University, Nara, Japan.
¹¹ Obesity Research Unit, Research Programs Unit, University of Helsinki, Helsinki, Finland.
¹² Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
¹³ Institute of Research and Development, Battaramulla, Sri Lanka.
¹⁴ Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka.
¹⁵ National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust, Institute of Psychiatry Psychology and Neuroscience.
¹⁶ Research Institute for Primary Care and Health Sciences, School for Primary Care Research, Faculty of Health, Keele University, Staffordshire, United Kingdom.
¹⁷ Medical Research Council Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, and.
¹⁸ Unit of Epidemiology, Biostatistics, and Biodemography, Departments of Public Health and.
¹⁹ Department of Public Health, Qingdao University Medical College, Qingdao, China.
²⁰ Department of Noncommunicable Diseases Prevention, Qingdao Centers for Disease Control and Prevention, Qingdao, China.
²¹ Institute for Molecular Medicine, Helsinki, Finland.
²² Public Health, and.
²³ Department of Statistics, Faculty of Arts and Sciences, Kırıkkale University, Kırıkkale, Turkey.
²⁴ Faculty of Business, Karabuk University, Karabuk, Turkey.
²⁵ Departments of Psychology and.
²⁶ African American Studies.
²⁷ The Danish Twin Registry.
²⁸ Departments of Clinical Biochemistry and Pharmacology and Clinical Genetics, and.
²⁹ Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁰ Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
³¹ Department of Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, and.
³² The Australian Twin Registry, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia.
³³ Department of Human Anatomy and Psychobiology, University of Murcia, Murcia, Spain.
³⁴ Biomedical Research Institute of Murcia (IMIB)-Arrixaca, Murcia, Spain.
³⁵ Quantitative Genetics Laboratory and.
³⁶ Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³⁷ Department of Epidemiology, School of Public Health, and.
³⁸ Institute of Health and Environment, Seoul National University, Seoul, South Korea.
³⁹ Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
⁴⁰ Department of Psychiatry, University of California, San Diego, CA.
⁴¹ US Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health, La Jolla, CA.
⁴² Department of Psychology, Boston University, Boston, MA.
⁴³ HealthTwiSt GmbH, Berlin, Germany.
⁴⁴ Department of Health and Exercise Sciences, Colorado School of Public Health, Colorado State University, Aurora, CO.
⁴⁵ Psychology Department, Wayne State University, Detroit, MI.
⁴⁶ Department of Psychology, Bielefeld University, Bielefeld, Germany.
⁴⁷ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Departments of.
⁴⁸ Department of Psychology, University of Southern California, Los Angeles, CA.
⁴⁹ Medical Epidemiology and Biostatistics and.
⁵⁰ Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine, Washington, DC.
⁵¹ Italian National Institute of Health National Center for Epidemiology, Surveillance, and Health Promotion, Rome, Italy.
⁵² Washington State Twin Registry, Health Sciences, Washington State University, Spokane, WA.
⁵³ Genetic Epidemiology Department, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia.
⁵⁴ Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
⁵⁵ Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.
⁵⁶ Center for Health Sciences, SRI International, Menlo Park, CA.
⁵⁷ Institute of Gerontology and Aging Research Network, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
⁵⁸ Department of Psychology, Goldsmiths, University of London, London, United Kingdom.
⁵⁹ Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
⁶⁰ School of Law, Psychology, and Social Work, Örebro University, Örebro, Sweden.
⁶¹ Healthy Twin Association of Mongolia, Ulaanbaatar, Mongolia.
⁶² Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁶³ Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
⁶⁴ National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom.
⁶⁵ Michigan State University, East Lansing, Michigan.
⁶⁶ Norwegian Institute of Public Health, Oslo, Norway.
⁶⁷ Department of Psychology, University of Minnesota, Minneapolis, MN.
⁶⁸ Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.
⁶⁹ Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands.
⁷⁰ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
⁷¹ Department of Radiology, Semmelweis University, Budapest, Hungary.
⁷² Hungarian Twin Registry, Budapest, Hungary.
⁷³ Centre of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
⁷⁴ Department of Obstetrics and Gynaecology, Ghent University Hospitals, Ghent, Belgium.
⁷⁵ Charles Bronfman Institute for Personalized Medicine, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷⁶ Departments of Human and Molecular Genetics and Psychiatry, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA.
⁷⁷ Department of Psychology, University of Virginia, Charlottesville, VA.
⁷⁸ Section on Metabolic Genetics, Novo Nordisk Foundation Centre for Basic Metabolic Research, Copenhagen, Denmark.
⁷⁹ Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and.
⁸⁰ Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, Copenhagen, Denmark.

PMID: 28679550
PMCID: PMC5525120
DOI: 10.3945/ajcn.117.153643

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.

Keywords: BMI; adults; genetics; international comparisons; twins.

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Figures

**FIGURE 1**
Additive genetic correlations for opposite-sex twin pairs by age based on maximum likelihood estimation. The number of opposite-sex pairs per age group is as follows: 7102 at 20–29 y, 6028 at 30–39 y, 5549 at 40–49 y, 6285 at 50–59 y, 3472 at 60–69 y, 1247 at 70–79 y, and 206 at ≥80 y.

**FIGURE 2**
Additive genetic and unique environmental variances in BMI by measurement year and sex based on maximum likelihood estimation. The number of complete twin pairs per decade varied from 3930 pairs in the 1960s to 22,055 pairs in the 2000s (the number of complete twin pairs by measurement year is available in Supplemental Table 3).

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References

1. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016;387:1377–96. - PMC - PubMed
1. Rokholm B, Baker JL, Sørensen TI. The levelling off of the obesity epidemic since the year 1999–a review of evidence and perspectives. Obes Rev 2010;11:835–46. - PubMed
1. Elks CE, den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJ, Ong KK. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol (Lausanne) 2012;3:29. - PMC - PubMed
1. Min J, Chiu DT, Wang Y. Variation in the heritability of body mass index based on diverse twin studies: a systematic review. Obes Rev 2013;14:871–82. - PMC - PubMed
1. Silventoinen K, Jelenkovic A, Sund R, Hur YM, Yokoyama Y, Honda C, Hjelmborg Jv, Möller S, Ooki S, Aaltonen S, et al. . Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study. Am J Clin Nutr 2016;104:371–9. - PMC - PubMed

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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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical