GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI

Alexessander Couto Alves; Maneka De Silva; Ville Karhunen; Ulla Sovio; Shikta Das; H Rob Taal; Nicole M. Warrington; Alex Lewin; Marika Kaakinen; Diana L. Cousminer; Elisabeth Thiering; Nicholas Timpson; Tom A Bond; Estelle Lowry; Christopher Brown; Xavier Estivill; Virpi Lindi; Jonathan P Bradfield; Frank Geller; Doug Speed; Lachlan J M Coin; Marie Loh; Sheila J Barton; Lawrence J Beilin; Hans Bisgaard; Klaus Bonnelykke; Rohia Alili; Ida Hatoum; Katharina Schramm; Rufus Cartwright; Marie-Aline Charles; Vincenzo Salerno; Karine Clement; Annique Claringbould; CM van Duijn; Elena Moltchanova; Timothy Frayling; Rachel Freathy; Debbie Lawlor; Susan Ring; George Davey Smith; Mark I McCarthy; Marjo-Riitta Järvelin; Early Growth Genetics (EGG) Consortium; BIOS Consortium

doi:10.1126/sciadv.aaw3095

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI

Alexessander Couto Alves, Maneka De Silva, Ville Karhunen, Ulla Sovio, Shikta Das, H Rob Taal, Nicole M. Warrington, Alex Lewin, Marika Kaakinen, Diana L. Cousminer, Elisabeth Thiering, Nicholas Timpson, Tom A Bond, Estelle Lowry, Christopher Brown, Xavier Estivill, Virpi Lindi, Jonathan P Bradfield, Frank Geller, Doug SpeedLachlan J M Coin, Marie Loh, Sheila J Barton, Lawrence J Beilin, Hans Bisgaard, Klaus Bonnelykke, Rohia Alili, Ida Hatoum, Katharina Schramm, Rufus Cartwright, Marie-Aline Charles, Vincenzo Salerno, Karine Clement, Annique Claringbould, CM van Duijn, Elena Moltchanova, Timothy Frayling, Rachel Freathy, Debbie Lawlor, Susan Ring, George Davey Smith, Mark I McCarthy, Marjo-Riitta Järvelin, Early Growth Genetics (EGG) Consortium, BIOS Consortium

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Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Original language	English
Article number	eaaw3095
Number of pages	18
Journal	Advances in Medical Sciences
Volume	5
Issue number	9
DOIs	https://doi.org/10.1126/sciadv.aaw3095
Publication status	Published - 4 Sept 2019

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
NIHR BRC Reproductive
Lawlor, D. A. (Principal Investigator)
1/04/17 → 30/11/22
Project: Research

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Alves, A. C., De Silva, M., Karhunen, V., Sovio, U., Das, S., Taal, H. R., Warrington, N. M., Lewin, A., Kaakinen, M., Cousminer, D. L., Thiering, E., Timpson, N., Bond, T. A., Lowry, E., Brown, C., Estivill, X., Lindi, V., Bradfield, J. P., Geller, F., ... BIOS Consortium (2019). GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI. Advances in Medical Sciences, 5(9), Article eaaw3095. https://doi.org/10.1126/sciadv.aaw3095

@article{becdb721f7664a9281f73dddacf47839,

title = "GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI",

abstract = "Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.",

author = "Alves, \{Alexessander Couto\} and \{De Silva\}, Maneka and Ville Karhunen and Ulla Sovio and Shikta Das and Taal, \{H Rob\} and Warrington, \{Nicole M.\} and Alex Lewin and Marika Kaakinen and Cousminer, \{Diana L.\} and Elisabeth Thiering and Nicholas Timpson and Bond, \{Tom A\} and Estelle Lowry and Christopher Brown and Xavier Estivill and Virpi Lindi and Bradfield, \{Jonathan P\} and Frank Geller and Doug Speed and Coin, \{Lachlan J M\} and Marie Loh and Barton, \{Sheila J\} and Beilin, \{Lawrence J\} and Hans Bisgaard and Klaus Bonnelykke and Rohia Alili and Ida Hatoum and Katharina Schramm and Rufus Cartwright and Marie-Aline Charles and Vincenzo Salerno and Karine Clement and Annique Claringbould and \{van Duijn\}, CM and Elena Moltchanova and Timothy Frayling and Rachel Freathy and Debbie Lawlor and Susan Ring and \{Davey Smith\}, George and McCarthy, \{Mark I\} and Marjo-Riitta J{\"a}rvelin and \{Early Growth Genetics (EGG) Consortium\} and \{BIOS Consortium\}",

year = "2019",

month = sep,

day = "4",

doi = "10.1126/sciadv.aaw3095",

language = "English",

volume = "5",

journal = "Advances in Medical Sciences",

issn = "1896-1126",

publisher = "Medical University of Bialystok",

number = "9",

}

Alves, AC, De Silva, M, Karhunen, V, Sovio, U, Das, S, Taal, HR, Warrington, NM, Lewin, A, Kaakinen, M, Cousminer, DL, Thiering, E, Timpson, N, Bond, TA, Lowry, E, Brown, C, Estivill, X, Lindi, V, Bradfield, JP, Geller, F, Speed, D, Coin, LJM, Loh, M, Barton, SJ, Beilin, LJ, Bisgaard, H, Bonnelykke, K, Alili, R, Hatoum, I, Schramm, K, Cartwright, R, Charles, M-A, Salerno, V, Clement, K, Claringbould, A, van Duijn, CM, Moltchanova, E, Frayling, T, Freathy, R, Lawlor, D , Ring, S , Davey Smith, G, McCarthy, MI, Järvelin, M-R, Early Growth Genetics (EGG) Consortium & BIOS Consortium 2019, 'GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI', Advances in Medical Sciences, vol. 5, no. 9, eaaw3095. https://doi.org/10.1126/sciadv.aaw3095

TY - JOUR

T1 - GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI

AU - Alves, Alexessander Couto

AU - De Silva, Maneka

AU - Karhunen, Ville

AU - Sovio, Ulla

AU - Das, Shikta

AU - Taal, H Rob

AU - Warrington, Nicole M.

AU - Lewin, Alex

AU - Kaakinen, Marika

AU - Cousminer, Diana L.

AU - Thiering, Elisabeth

AU - Timpson, Nicholas

AU - Bond, Tom A

AU - Lowry, Estelle

AU - Brown, Christopher

AU - Estivill, Xavier

AU - Lindi, Virpi

AU - Bradfield, Jonathan P

AU - Geller, Frank

AU - Speed, Doug

AU - Coin, Lachlan J M

AU - Loh, Marie

AU - Barton, Sheila J

AU - Beilin, Lawrence J

AU - Bisgaard, Hans

AU - Bonnelykke, Klaus

AU - Alili, Rohia

AU - Hatoum, Ida

AU - Schramm, Katharina

AU - Cartwright, Rufus

AU - Charles, Marie-Aline

AU - Salerno, Vincenzo

AU - Clement, Karine

AU - Claringbould, Annique

AU - van Duijn, CM

AU - Moltchanova, Elena

AU - Frayling, Timothy

AU - Freathy, Rachel

AU - Lawlor, Debbie

AU - Ring, Susan

AU - Davey Smith, George

AU - McCarthy, Mark I

AU - Järvelin, Marjo-Riitta

AU - Early Growth Genetics (EGG) Consortium

AU - BIOS Consortium

PY - 2019/9/4

Y1 - 2019/9/4

N2 - Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

AB - Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

U2 - 10.1126/sciadv.aaw3095

DO - 10.1126/sciadv.aaw3095

M3 - Article (Academic Journal)

C2 - 31840077

SN - 1896-1126

VL - 5

JO - Advances in Medical Sciences

JF - Advances in Medical Sciences

IS - 9

M1 - eaaw3095

ER -

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

NIHR BRC Reproductive

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