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Article Dans Une Revue PLoS Genetics Année : 2020

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Suzanne Vogelezang (1) , Jonathan Bradfield (2) , Tarunveer Ahluwalia (3) , John Curtin (4) , Timo Lakka (5) , Niels Grarup (6) , Markus Scholz (7) , Peter van Der Most (8) , Claire Monnereau (1) , Evie Stergiakouli (9) , Anni Heiskala (10) , Momoko Horikoshi (11) , Iryna Fedko (12) , Natalia Vilor-Tejedor (13) , Diana Cousminer (2) , Marie Standl (14) , Carol Wang (15) , Jorma Viikari (16) , Frank Geller (17) , Carmen Íñiguez (13) , Niina Pitkänen (16) , Alessandra Chesi (2) , Jonas Bacelis (18) , Loic Yengo (19) , Maties Torrent , Ioanna Ntalla (20) , Øyvind Helgeland (21) , Saskia Selzam (22) , Judith Vonk (23) , Mohammed Zafarmand (24) , Barbara Heude (25) , Ismaa Sadaf Farooqi (26) , Akram Alyass (27) , Robin Beaumont (28) , Christian Have (6) , Peter Rzehak (29) , Jose Ramon Bilbao (30) , Theresia Schnurr (6) , Inês Barroso (31) , Klaus Bønnelykke (6) , Lawrence Beilin (32) , Lisbeth Carstensen (17) , Marie-Aline Charles (25) , Bo Chawes (6) , Karine Clément (33) , Ricardo Closa-Monasterolo (34) , Adnan Custovic (35) , Johan Eriksson (36) , Joaquin Escribano (34) , Maria Groen-Blokhuis (37) , Veit Grote (29) , Dariusz Gruszfeld , Hakon Hakonarson (2) , Torben Hansen (6) , Andrew Hattersley (28) , Mette Hollensted (6) , Jouke-Jan Hottenga (37) , Elina Hyppönen (38) , Stefan Johansson (39) , Raimo Joro (5) , Mika Kähönen (40) , Ville Karhunen (35) , Wieland Kiess (7) , Bridget Knight (28) , Berthold Koletzko (29) , Andreas Kühnapfel (7) , Kathrin Landgraf (7) , Jean-Paul Langhendries , Terho Lehtimäki (40) , Jaakko Leinonen (36) , Aihuali Li (27) , Virpi Lindi (5) , Estelle Lowry (41) , Mariona Bustamante (13) , Carolina Medina-Gomez (1) , Mads Melbye (17) , Kim Michaelsen (6) , Camilla Morgen (6) , Trevor Mori (32) , Tenna Nielsen (42) , Harri Niinikoski (43) , Albertine Oldehinkel (23) , Katja Pahkala (43) , Kalliope Panoutsopoulou (31) , Oluf Pedersen (6) , Craig Pennell (15) , Christine Power (38) , Sijmen Reijneveld (23) , Fernando Rivadeneira (1) , Angela Simpson (44) , Peter Sly (45) , Jakob Stokholm (6) , Kook Teo (27) , Elisabeth Thiering (29) , Nicholas Timpson (9) , André Uitterlinden (1) , Catharina van Beijsterveldt (37) , Barbera van Schaik (24) , Marc Vaudel (46) , Elvira Verduci (47) , Rebecca Vinding (6) , Mandy Vogel (7) , Eleftheria Zeggini (31) , Sylvain Sebert , Mads Lind , Christopher Brown , Loreto Santa-Marina , Eva Reischl , Christine Frithioff-Bøjsøe , David Meyre , Eleanor Wheeler , Ken Ong , Ellen Nohr , Tanja Vrijkotte , Gerard Koppelman , Robert Plomin , Pål Njølstad , George Dedoussis , Philippe Froguel (19, 35) , Thorkild Sørensen , Bo Jacobsson , Rachel Freathy , Babette Zemel , Olli Raitakari , Martine Vrijheid , Bjarke Feenstra , Leo-Pekka Lyytikäinen , Harold Snieder , Holger Kirsten , Patrick Holt , Joachim Heinrich , Elisabeth Widén , Jordi Sunyer , Dorret Boomsma , Marjo-Riitta Järvelin , Antje Körner , George Davey Smith , Jens-Christian Holm , Mustafa Atalay , Clare Murray , Hans Bisgaard , Mark Mccarthy , Vincent Jaddoe , Struan Grant , Janine Felix
1 Erasmus MC - Erasmus University Medical Center [Rotterdam]
2 CHOP - Children’s Hospital of Philadelphia
3 Herlev and Gentofte Hospital
4 MAHSC - Manchester Academic Health Science Centre
5 University of Kuopio
6 UCPH - University of Copenhagen = Københavns Universitet
7 Leipzig University / Universität Leipzig
8 UMCG - University Medical Center Groningen [Groningen]
9 University of Bristol [Bristol]
10 Université d'Oulu
11 The Wellcome Trust Centre for Human Genetics [Oxford]
12 VUB - Vrije Universiteit Brussel
13 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
14 Helmholtz Zentrum München = German Research Center for Environmental Health
15 UoN - University of Newcastle [Callaghan, Australia]
16 TYKS - Turku University Hospital
17 Statens Serum Institut [Copenhagen]
18 Sahlgrenska Academy at University of Gothenburg [Göteborg]
19 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
20 QMUL - Queen Mary University of London
21 NIPH - Norwegian Institute of Public Health [Oslo]
22 King‘s College London
23 University of Groningen [Groningen]
24 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
25 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
26 CAM - University of Cambridge [UK]
27 McMaster University [Hamilton, Ontario]
28 University of Exeter
29 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
30 UPV / EHU - University of the Basque Country = Euskal Herriko Unibertsitatea
31 The Wellcome Trust Sanger Institute [Cambridge]
32 UWA - The University of Western Australia
33 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
34 Universitat Rovira i Virgili
35 Imperial College London
36 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
37 VU - Vrije Universiteit Amsterdam [Amsterdam]
38 UCL - University College of London [London]
39 UiB - University of Bergen
40 University of Tampere [Finland]
41 University of Oulu
42 Copenhagen University Hospital
43 University of Turku
44 University of Manchester [Manchester]
45 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
46 Haukeland University Hospital
47 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
Timo Lakka
  • Fonction : Auteur
Anni Heiskala
  • Fonction : Auteur
Maties Torrent
  • Fonction : Auteur
Dariusz Gruszfeld
Hakon Hakonarson
Raimo Joro
  • Fonction : Auteur
Mika Kähönen
Jean-Paul Langhendries
  • Fonction : Auteur
Virpi Lindi
  • Fonction : Auteur
Estelle Lowry
  • Fonction : Auteur
Sylvain Sebert
  • Fonction : Auteur
Mads Lind
  • Fonction : Auteur
Christopher Brown
  • Fonction : Auteur
Loreto Santa-Marina
  • Fonction : Auteur
Eva Reischl
  • Fonction : Auteur
Christine Frithioff-Bøjsøe
  • Fonction : Auteur
David Meyre
Eleanor Wheeler
  • Fonction : Auteur
Ken Ong
  • Fonction : Auteur
Ellen Nohr
  • Fonction : Auteur
Tanja Vrijkotte
  • Fonction : Auteur
Gerard Koppelman
  • Fonction : Auteur
Robert Plomin
  • Fonction : Auteur
Pål Njølstad
  • Fonction : Auteur
George Dedoussis
Thorkild Sørensen
  • Fonction : Auteur
Bo Jacobsson
Rachel Freathy
  • Fonction : Auteur
Babette Zemel
  • Fonction : Auteur
Olli Raitakari
  • Fonction : Auteur
Martine Vrijheid
Bjarke Feenstra
  • Fonction : Auteur
Leo-Pekka Lyytikäinen
  • Fonction : Auteur
Harold Snieder
  • Fonction : Auteur
Holger Kirsten
  • Fonction : Auteur
Patrick Holt
  • Fonction : Auteur
Joachim Heinrich
  • Fonction : Auteur
Elisabeth Widén
  • Fonction : Auteur
Jordi Sunyer
  • Fonction : Auteur
Dorret Boomsma
  • Fonction : Auteur
Marjo-Riitta Järvelin
  • Fonction : Auteur
Antje Körner
  • Fonction : Auteur
George Davey Smith
  • Fonction : Auteur
Jens-Christian Holm
  • Fonction : Auteur
Mustafa Atalay
  • Fonction : Auteur
Clare Murray
  • Fonction : Auteur
Hans Bisgaard
  • Fonction : Auteur
Mark Mccarthy
  • Fonction : Auteur
Vincent Jaddoe
  • Fonction : Auteur
Struan Grant
  • Fonction : Auteur
Janine Felix

Résumé

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.
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hal-03269687 , version 1 (28-06-2021)

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Suzanne Vogelezang, Jonathan Bradfield, Tarunveer Ahluwalia, John Curtin, Timo Lakka, et al.. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genetics, 2020, 16 (10), pp.e1008718. ⟨10.1371/journal.pgen.1008718⟩. ⟨hal-03269687⟩
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