Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

Karri Silventoinen; Weilong Li; Aline Jelenkovic; Reijo Sund; Yoshie Yokoyama; Sari Aaltonen; Maarit Piirtola; Masumi Sugawara; Mami Tanaka; Satoko Matsumoto; Laura A. Baker; Catherine Tuvblad; Per Tynelius; Finn Rasmussen; Jeffrey M. Craig; Richard Saffery; Gonneke Willemsen; Meike Bartels; Catharina E.M. van Beijsterveldt; Nicholas G. Martin; Sarah E. Medland; Grant W. Montgomery; Paul Lichtenstein; Robert F. Krueger; Matt McGue; Shandell Pahlen; Kaare Christensen; Axel Skytthe; Kirsten O. Kyvik; Kimberly J. Saudino; Lise Dubois; Michel Boivin; Mara Brendgen; Ginette Dionne; Frank Vitaro; Vilhelmina Ullemar; Catarina Almqvist; Patrik K.E. Magnusson; Robin P. Corley; Brooke M. Huibregtse; Ariel Knafo-Noam; David Mankuta; Lior Abramson; Claire M.A. Haworth; Robert Plomin; Morten Bjerregaard-Andersen; Henning Beck-Nielsen; Morten Sodemann; Glen E. Duncan; Dedra Buchwald; S. Alexandra Burt; Kelly L. Klump; Clare H. Llewellyn; Abigail Fisher; Dorret I. Boomsma; Thorkild I.A. Sørensen; Jaakko Kaprio

doi:10.1038/s41366-022-01202-3

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

Karri Silventoinen^*
, Weilong Li
, Aline Jelenkovic
, Reijo Sund
, Yoshie Yokoyama
, Sari Aaltonen
, Maarit Piirtola
, Masumi Sugawara
, Mami Tanaka
, Satoko Matsumoto
, Laura A. Baker
, Catherine Tuvblad
, Per Tynelius
, Finn Rasmussen
, Jeffrey M. Craig
, Richard Saffery
, Gonneke Willemsen
, Meike Bartels
, Catharina E.M. van Beijsterveldt
, Nicholas G. Martin

Sarah E. Medland, Grant W. Montgomery, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Vilhelmina Ullemar, Catarina Almqvist, Patrik K.E. Magnusson, Robin P. Corley, Brooke M. Huibregtse, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Claire M.A. Haworth, Robert Plomin, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Glen E. Duncan, Dedra Buchwald, S. Alexandra Burt, Kelly L. Klump, Clare H. Llewellyn, Abigail Fisher, Dorret I. Boomsma, Thorkild I.A. Sørensen, Jaakko Kaprio

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Original language	English
Pages (from-to)	1901-1909
Number of pages	9
Journal	International Journal of Obesity
Volume	46
Issue number	10
Early online date	9 Aug 2022
DOIs	https://doi.org/10.1038/s41366-022-01202-3
Publication status	Published - 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

This study was conducted within the CODATwins project. Support for collaborators: Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longititudinal Twin Study HD10333; Author Huibregtse is supported by National Institute on Drug Abuse (5T32DA017637) and National Institute on Aging (5T32AG052371). Finnish Twin Cohort is supported by the Academy of Finland (grants 312073 and 336823) and the Sigrid Juselius Foundation. Michigan State University Twin Registry was supported by National Institute of Mental Health (NIMH) (R01-MH081813, R01-MH0820–54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01, 1R01-MH118848-01), Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) (R01-HD066040) and MSU Foundation (11-SPG-2518). PETS was funded by the Australian National Health and Medical Research Council (grant numbers 437015 and 607358); the Bonnie Babes Foundation (grant number BBF20704); the Financial Markets Foundation for Children (grant number 032-2007); and the Victorian Government’s Operational Infrastructure Support Program. We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. TEDS was supported by a program grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 20H04019) from the Japan Society for the Promotion of Science. Open Access funding provided by University of Helsinki including Helsinki University Central Hospital.

Funders	Funder number
Eunice Kennedy Shriver National Institute of Child Health and Human Development
State Government of Victoria
Karolinska Institutet
Sigrid Juséliuksen Säätiö
UK Research and Innovation
National Institute of Mental Health	R01MH081813, R21-MH070542-01, R01MH092377, 1R01-MH118848-01, R03-MH63851-01, R01-MH0820–54
Japan Society for the Promotion of Science	20H00106
Academy of Finland	312073, 336823
National Institute on Drug Abuse	DA011015, T32DA017637, HD10333
National Health and Medical Research Council	437015, 607358
National Institute on Aging	T32AG052371
Financial Markets Foundation for Children	032-2007
Michigan State University Foundation	11-SPG-2518
National Institutes of Health	20H04019, AG046938
Bonnie Babes Foundation	BBF20704
Medical Research Council	G0901245, MR/M021475/1
National Institute of Child Health and Human Development	R01HD066040
Vetenskapsrådet	2017-00641

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41366-022-01202-3

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Silventoinen, K., Li, W., Jelenkovic, A., Sund, R., Yokoyama, Y., Aaltonen, S., Piirtola, M., Sugawara, M., Tanaka, M., Matsumoto, S., Baker, L. A., Tuvblad, C., Tynelius, P., Rasmussen, F., Craig, J. M., Saffery, R., Willemsen, G., Bartels, M., van Beijsterveldt, C. E. M., ... Kaprio, J. (2022). Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts. International Journal of Obesity, 46(10), 1901-1909. https://doi.org/10.1038/s41366-022-01202-3

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title = "Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts",

abstract = "Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.",

author = "Karri Silventoinen and Weilong Li and Aline Jelenkovic and Reijo Sund and Yoshie Yokoyama and Sari Aaltonen and Maarit Piirtola and Masumi Sugawara and Mami Tanaka and Satoko Matsumoto and Baker, \{Laura A.\} and Catherine Tuvblad and Per Tynelius and Finn Rasmussen and Craig, \{Jeffrey M.\} and Richard Saffery and Gonneke Willemsen and Meike Bartels and \{van Beijsterveldt\}, \{Catharina E.M.\} and Martin, \{Nicholas G.\} and Medland, \{Sarah E.\} and Montgomery, \{Grant W.\} and Paul Lichtenstein and Krueger, \{Robert F.\} and Matt McGue and Shandell Pahlen and Kaare Christensen and Axel Skytthe and Kyvik, \{Kirsten O.\} and Saudino, \{Kimberly J.\} and Lise Dubois and Michel Boivin and Mara Brendgen and Ginette Dionne and Frank Vitaro and Vilhelmina Ullemar and Catarina Almqvist and Magnusson, \{Patrik K.E.\} and Corley, \{Robin P.\} and Huibregtse, \{Brooke M.\} and Ariel Knafo-Noam and David Mankuta and Lior Abramson and Haworth, \{Claire M.A.\} and Robert Plomin and Morten Bjerregaard-Andersen and Henning Beck-Nielsen and Morten Sodemann and Duncan, \{Glen E.\} and Dedra Buchwald and Burt, \{S. Alexandra\} and Klump, \{Kelly L.\} and Llewellyn, \{Clare H.\} and Abigail Fisher and Boomsma, \{Dorret I.\} and S{\o}rensen, \{Thorkild I.A.\} and Jaakko Kaprio",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

doi = "10.1038/s41366-022-01202-3",

language = "English",

volume = "46",

pages = "1901--1909",

journal = "International Journal of Obesity",

issn = "0307-0565",

publisher = "Springer Nature",

number = "10",

}

Silventoinen, K, Li, W, Jelenkovic, A, Sund, R, Yokoyama, Y, Aaltonen, S, Piirtola, M, Sugawara, M, Tanaka, M, Matsumoto, S, Baker, LA, Tuvblad, C, Tynelius, P, Rasmussen, F, Craig, JM, Saffery, R, Willemsen, G, Bartels, M, van Beijsterveldt, CEM, Martin, NG, Medland, SE, Montgomery, GW, Lichtenstein, P, Krueger, RF, McGue, M, Pahlen, S, Christensen, K, Skytthe, A, Kyvik, KO, Saudino, KJ, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Ullemar, V, Almqvist, C, Magnusson, PKE, Corley, RP, Huibregtse, BM, Knafo-Noam, A, Mankuta, D, Abramson, L, Haworth, CMA, Plomin, R, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Duncan, GE, Buchwald, D, Burt, SA, Klump, KL, Llewellyn, CH, Fisher, A, Boomsma, DI, Sørensen, TIA & Kaprio, J 2022, 'Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts', International Journal of Obesity, vol. 46, no. 10, pp. 1901-1909. https://doi.org/10.1038/s41366-022-01202-3

TY - JOUR

T1 - Changing genetic architecture of body mass index from infancy to early adulthood

T2 - an individual based pooled analysis of 25 twin cohorts

AU - Silventoinen, Karri

AU - Li, Weilong

AU - Jelenkovic, Aline

AU - Sund, Reijo

AU - Yokoyama, Yoshie

AU - Aaltonen, Sari

AU - Piirtola, Maarit

AU - Sugawara, Masumi

AU - Tanaka, Mami

AU - Matsumoto, Satoko

AU - Baker, Laura A.

AU - Tuvblad, Catherine

AU - Tynelius, Per

AU - Rasmussen, Finn

AU - Craig, Jeffrey M.

AU - Saffery, Richard

AU - Willemsen, Gonneke

AU - Bartels, Meike

AU - van Beijsterveldt, Catharina E.M.

AU - Martin, Nicholas G.

AU - Medland, Sarah E.

AU - Montgomery, Grant W.

AU - Lichtenstein, Paul

AU - Krueger, Robert F.

AU - McGue, Matt

AU - Pahlen, Shandell

AU - Christensen, Kaare

AU - Skytthe, Axel

AU - Kyvik, Kirsten O.

AU - Saudino, Kimberly J.

AU - Dubois, Lise

AU - Boivin, Michel

AU - Brendgen, Mara

AU - Dionne, Ginette

AU - Vitaro, Frank

AU - Ullemar, Vilhelmina

AU - Almqvist, Catarina

AU - Magnusson, Patrik K.E.

AU - Corley, Robin P.

AU - Huibregtse, Brooke M.

AU - Knafo-Noam, Ariel

AU - Mankuta, David

AU - Abramson, Lior

AU - Haworth, Claire M.A.

AU - Plomin, Robert

AU - Bjerregaard-Andersen, Morten

AU - Beck-Nielsen, Henning

AU - Sodemann, Morten

AU - Duncan, Glen E.

AU - Buchwald, Dedra

AU - Burt, S. Alexandra

AU - Klump, Kelly L.

AU - Llewellyn, Clare H.

AU - Fisher, Abigail

AU - Boomsma, Dorret I.

AU - Sørensen, Thorkild I.A.

AU - Kaprio, Jaakko

PY - 2022

Y1 - 2022

N2 - Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

AB - Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

UR - https://www.scopus.com/pages/publications/85135772911

UR - https://www.scopus.com/pages/publications/85135772911#tab=citedBy

U2 - 10.1038/s41366-022-01202-3

DO - 10.1038/s41366-022-01202-3

M3 - Article

C2 - 35945263

AN - SCOPUS:85135772911

SN - 0307-0565

VL - 46

SP - 1901

EP - 1909

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 10

ER -

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

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