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The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study

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Mohamed Abdulkadir, Christopher Hübel, Moritz Herle, Ruth J F Loos, Gerome Breen, Cynthia M Bulik, Nadia Micali

Original languageEnglish
Pages (from-to)1242-1254
Number of pages13
JournalAmerican Journal of Human Genetics
Volume109
Issue number7
Early online date8 Jun 2022
DOIs
E-pub ahead of print8 Jun 2022
Published7 Jul 2022

Bibliographical note

Funding Information: We are extremely grateful to all of the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. This study represents independent research partly funded by the UK National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. High-performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). This work was supported by the UK Medical Research Council and the Medical Research Foundation (MR/R004803/1). The UK Medical Research Council and Wellcome (102215/2/13/2 and 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants is available on the ALSPAC website. This research was specifically funded by the NIHR (CS/01/2008/014) and the NIH (MH087786-01). GWAS data were generated by sample logistics and genotyping facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. N.M. and C.M.B. acknowledge funding from the National Institute of Mental Health (R21 MH115397). C.M.B. is supported by NIMH (R01MH120170, R01MH124871, R01MH119084, R01MH118278, R01 MH124871), Brain and Behavior Research Foundation Distinguished Investigator Grant, Swedish Research Council (Vetenskapsrådet, 538-2013-8864), and Lundbeck Foundation (R276-2018-4581). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the UK NHS, the NIHR, or the Department of Health. The funders were not involved in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. M.A. C.H. and M.H. analyzed the data. M.A. C.H. and M.H. drafted the manuscript. N.M. C.M.B. R.J.F.L. and G.B. supervised the work. All authors substantially contributed to the conception and interpretation of the work, revised the manuscript for important intellectual content, and approved the final version. All authors agree to be accountable for all aspects of this work. G.B. has received grant funding from and served as a consultant to Eli Lilly, has received honoraria from Illumina, and has served on advisory boards for Otsuka. C.M.B. is a grant recipient from and has served on advisory boards for Takeda/Shire and is a consultant for Idorsia. She receives royalties from Pearson. She is on the Clinical Advisory Board of Equip Health Inc. Funding Information: We are extremely grateful to all of the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. This study represents independent research partly funded by the UK National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. High-performance computing facilities were funded with capital equipment grants from the GSTT Charity ( TR130505 ) and Maudsley Charity ( 980 ). This work was supported by the UK Medical Research Council and the Medical Research Foundation ( MR/R004803/1 ). The UK Medical Research Council and Wellcome ( 102215/2/13/2 and 217065/Z/19/Z ) and the University of Bristol provide core support for ALSPAC . A comprehensive list of grants is available on the ALSPAC website. This research was specifically funded by the NIHR ( CS/01/2008/014 ) and the NIH ( MH087786-01 ). GWAS data were generated by sample logistics and genotyping facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. N.M. and C.M.B. acknowledge funding from the National Institute of Mental Health ( R21 MH115397 ). C.M.B. is supported by NIMH ( R01MH120170 , R01MH124871 , R01MH119084 , R01MH118278 , R01 MH124871 ), Brain and Behavior Research Foundation Distinguished Investigator Grant, Swedish Research Council (Vetenskapsrådet, 538-2013-8864 ), and Lundbeck Foundation ( R276-2018-4581 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the UK NHS, the NIHR, or the Department of Health. The funders were not involved in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. Publisher Copyright: © 2022 The Authors

King's Authors

Abstract

Growth deviating from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life. AN PGSs and BMI PGSs were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Female participants with AN PGSs one standard deviation (SD) higher had, on average, 0.004% slower growth in BMI between the ages 6.5 and 24 years and a 0.4% slower gain in BMD between the ages 10 and 24 years. Higher BMI PGSs were associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN PGS and a low BMI PGS showed slower growth compared to those with both a low AN PGS and a low BMI PGS. We conclude that AN PGSs and BMI PGSs have detectable sex-specific effects on growth trajectories. Female participants with a high AN PGS and low BMI PGS likely constitute a high-risk group for AN, as their growth was slower compared to their peers with high PGSs on both traits. Further research is needed to better understand how the AN PGS and the BMI PGS co-influence growth during childhood and whether a high BMI PGS can mitigate the effects of a high AN PGS.

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