Genetic and environmental factors affecting birth size variation: A pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts

Yoshie Yokoyama*, Aline Jelenkovic, Yoon Mi Hur, Reijo Sund, Corrado Fagnani, Maria A. Stazi, Sonia Brescianini, Fuling Ji, Feng Ning, Zengchang Pang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Esther Rebato, John L. Hopper, Tessa L. Cutler, Kimberly J. Saudino, Tracy L. Nelson, Keith E. Whitfield, Robin P. CorleyBrooke M. Huibregtse, Catherine A. Derom, Robert F. Vlietinck, Ruth J.F. Loos, Clare H. Llewellyn, Abigail Fisher, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Robert F. Krueger, Matt McGue, Shandell Pahlen, Meike Bartels, Catharina E.M. Van Beijsterveldt, Gonneke Willemsen, Jennifer R. Harris, Ingunn Brandt, Thomas S. Nilsen, Jeffrey M. Craig, Richard Saffery, Lise Dubois, Michel Boivin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Claire M.A. Haworth, Robert Plomin, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Finn Rasmussen, Per Tynelius, Adam D. Tarnoki, David L. Tarnoki, Syuichi Ooki, Richard J. Rose, Kirsi H. Pietiläinen, Thorkild I.A. Sørensen, Dorret I. Boomsma, Jaakko Kaprio, Karri Silventoinen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.

Original languageAmerican English
Pages (from-to)1195-1206
Number of pages12
JournalInternational Journal of Epidemiology
Issue number4
StatePublished - 1 Aug 2018

Bibliographical note

Funding Information:
Figure 3. Total, additive genetic, shared environmental and unique environmental variances of birthweight by twin cohort. Au, Australian Twin Registry; Bo: Boston University Twin Project; Ca, Carolina African American Twin Study of Aging; Co, Colorado Twin Registry; EF, East Flanders Prospective Twin Survey; F12, Finntwin12; F16, Finntwin16; Ge, Gemini Study; GB, Guinea-Bissau Twin Study; Hu, Hungarian Twin Registry; It, Italian Twin Registry; Ja, Japanese Twin Cohort; Is, Longitudinal Israeli Study of Twins; Mi, Michigan Twins Study; MinC, Minnesota Twin Family Study; MinA, Minnesota Twin Registry; Mo, Mongolian Twin Registry; No, Norwegian Twin Registry; PETS, Peri/Postnatal Epigenetic Twins Study; Qi, Qingdao Twin Registry of Children; Qu, Quebec Newborn Twin Study; SwA, Swedish Young Male Twins Study of Adults; SwC, Swedish Young Male Twins Study of Children; TEDS, Twins Early Developmental Study; WJ, West Japan Twins and Higher Order Multiple Births Registry; Ne, Young Netherlands Twin Registry.

Funding Information:
This study was conducted within the CODATwins project (Academy of Finland #266592). The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council, administered by the University of Melbourne. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K.J.S. The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662– 01A2) to KE.W. The Colorado Twin Registry is funded by NIDA-funded centre grant DA011015, & Longitudinal Twin Study HD10333; B.M.H. is supported by 5T32DA017637–11. Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE—European Network for Genetic and Genomic Epidemiology—FP7-HEALTH-F4–2007, grant agreement number 201413, the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R.J.R., the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J.K.). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd, Budapest, Hungary. The Italian Twin Registry was partially supported by the Chiesi Foundation. The Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to A.K. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820– 54, R01-MH092377–02, R21-MH070542–01 and R03-MH63851– 01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. Data collection and research stemming from the Norwegian Twin Registry are supported, in part, by the European Union’s Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4–2007-201413, and BioSHaRE EU (grant agreement HEALTH-F4–2010-261433). The Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904–61-090, 985–10-002, 912–10-020, 904–61-193, 480–

Funding Information:
04-004, 463–06-001, 451–04-034, 400–05-717, Addiction-31160008, Middelgroot-911–09-032, Spinozapremie 56–464-14192; VU University’s Institute for Health and Care Research (EMGO+ ); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to J.C. and R.S.), the Bonnie Babes Foundation (grant number BBF20704 to J.M.C.), the Financial Markets Foundation for Children (grant no. 032–2007 to J.M.C.) and by the Victorian Government’s Operational Infrastructure Support Program. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Québécois de la Recherche sur la Société et la Culture, the Fonds de la Recherche en Santé du Québec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital’s Research Center and the Canada Research Chair Program (Michel Boivin). The Twins Early Development Study (TEDS) is supported by a programme grant (G0901245) from the UK Medical Research Council, and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/ D19086). Currently TEDS is supported by MRC grant ‘MR/ M021475/1’. The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

Publisher Copyright:
© 2018 Oxford University Press. All Rights Reserved.


  • Birth length
  • Birthweight
  • Genetics
  • Ponderal index
  • Pooled studies
  • Twins


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