Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

6533b7dcfe1ef96bd1272998

RESEARCH PRODUCT

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

D. L. Cousminer D. J. Berry N. J. Timpson W. Ang E. Thiering E. M. Byrne H. R. Taal V. Huikari J. P. Bradfield M. Kerkhof M. M. Groen Blokhuis E. Kreiner Moller M. Marinelli C. Holst J. T. Leinonen J. R. B. Perry I. Surakka O. Pietilainen J. Kettunen V. Anttila M. Kaakinen U. Sovio A. Pouta S. Das V. Lagou C. Power I. Prokopenko D. M. Evans J. P. Kemp B. St Pourcain S. Ring A. Palotie E. Kajantie C. Osmond T. Lehtimaki J. S. Viikari M. Kahonen N. M. Warrington S. J. Lye L. J. Palmer C. M. T. Tiesler C. Flexeder G. W. Montgomery S. E. Medland A. Hofman H. Hakonarson M. Guxens M. Bartels V. Salomaa J. M. Murabito J. Kaprio T. I. A. Sorensen F. Ballester Hans Bisgaard D. I. Boomsma G. H. Koppelman S. F. A. Grant V. W. V. Jaddoe N. G. Martin J. Heinrich C. E. Pennell O. T. Raitakari J. G. Eriksson G. D. Smith E. Hypponen M. R. Jarvelin M. I. Mccarthy S. Ripatti E. Widen Adair Ls Ang W Atalay M Van Beijsterveldt T Bergen N Benke K Berry Dj Boomsma Di Bradfield Jp Charoen P Coin L Cooper C Cousminer Dl Das S Davis Os Dedoussis Gv Elliott P Estivill X Evans Dm Feenstra B Flexeder C Frayling T Freathy Rm Gaillard R Geller F Gillman M Grant Sf Groen Blokhuis M Goh Lk Guxens M Hakonarson H Hattersley At Haworth Cm Hadley D Hedebrand J Heinrich J Hinney A Hirschhorn Jn Hocher B Holloway Jw Holst C Hottenga Jj Horikoshi M Huikari V Hypponen E Iñiguez C Jaddoe Vw Jarvelin Mr Kaakinen M Kilpeläinen To Kirin M Kowgier M Lakka Hm Lakka Ta Lange La Lawlor Da Lehtimäki T Lewin A Lindgren C Lindi V Maggi R Marsh J Mccarthy Mi Melbye M Middeldorp C Millwood I Mohlke Kl Mook Kanamori Do Murray Jc Nivard M Nohr Ea Ntalla I Oken E Ong Kk O'reilly Pf Palmer Lj Panoutsopoulou K Pararajasingham J Pearson Er Pennell Ce Power C Price Ts Prokopenko I Raitakari Ot Rodriguez A Salem Rm Saw Sm Scherag A Sebert S Siitonen N Simell O Sørensen Ti Sovio U Pourcain Bs Strachan Dp Sunyer J Taal Hr Teo Yy Thiering E Tiesler C Timpson Nj Uitterlinden Ag Valcárcel B Warrington Nm White S Widén E Willemsen G Wilson Jf Yaghootkar H Zeggini E Elks Ce Perry Jr Sulem P Chasman Di Franceschini N He C Lunetta Kl Visser Ja Byrne Em Cousminer Dl Gudbjartsson Df Esko T Feenstra B Hottenga Jj Koller Dl Kutalik Z Lin P Mangino M Marongiu M Mcardle Pf Smith Av Stolk L Van Wingerden Sh Zhao Jh Albrecht E Corre T Ingelsson E Hayward C Magnusson Pk Smith En Ulivi S Warrington M Zgaga L Alavere H Amin N Aspelund T Bandinelli S Barroso I Berenson Gs Bergmann S Blackburn H Boerwinkle E Buring Je Busonero F Campbell H Chanock Sj Chen W Cornelis Mc Couper D Coviello Ad De Faire U De Geus Ej Deloukas P Döring A Davey Smith G Easton Df Eiriksdottir G Emilsson V Eriksson J Ferrucci L Folsom Ar Foroud T Garcia M Paolo Gasparini Geller F Gieger C Gudnason V Hall P Hankinson Se Ferreli L Heath Ac Hernandez Dg Hofman A Hu Fb Illig T Järvelin Mr Johnson Ad Karasik D Khaw Kt Kiel Dp Kilpeläinen To Kolcic I Kraft P Launer Lj Laven Js Li S Liu J Levy D Martin Ng Mcardle Wl Melbye M Mooser V Murray Jc Murray Ss Nalls Ma Navarro P Nelis M Ness Ar Northstone K Oostra Ba Peacock M Palmer Lj Palotie A Paré G Parker An Pedersen Nl Peltonen L Pennell Ce Pharoah P Polasek O Plump As Pouta A Porcu E Rafnar T Rice Jp Ring Sm Rivadeneira F Rudan I Sala C Salomaa V Sanna S Schlessinger D Schork Nj Scuteri A Segrè Av Shuldiner Ar Soranzo N Sovio U Srinivasan Sr Strachan Dp Tammesoo Ml Tikkanen E Toniolo D Tsui K Tryggvadottir L Tyrer J Uda M Van Dam Rm Van Meurs Jb Vollenweider P Waeber G Wareham Nj Waterworth Dm Weedon Mn Wichmann He Willemsen G Wilson Jf Wright Af Young L Zhai G Zhuang Wv Bierut Lj Boyd Ha Crisponi L Demerath Ew Van Duijn Cm Econs Mj Harris Tb Hunter Dj Loos Rj Metspalu A Montgomery Gw Ridker Pm Spector Td Streeten Ea Stefansson K Thorsteinsdottir U Uitterlinden Ag Widen E Murabito Jm Ong Kk Murray A.Adamo Pio D'adamo

subject

Male Netherlands Twin Register (NTR)Genetic Linkage Medizin Gene Expression Genome-wide association study VARIANTS Body Mass Index 0302 clinical medicine genetic linkage Transforming Growth Factor beta Neoplasms molecular biology genetics Child Genetics (clinical)Adiposity 2. Zero hunger 0303 health sciences adiposity Mitogen-Activated Protein Kinase 3 Association Studies Articles Age Factors ACHONDROPLASIA General Medicine Genome-Wide Association Study; pubertal height growth; pubertal timing Phenotype OBESITY Menarche /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being body height Female Signal Transduction medicine.medical_specialty age factors CHROMOSOME 16P11.2 Adolescent BIRTH Quantitative Trait Loci 030209 endocrinology & metabolism Context (language use)Biology Childhood obesity pubertal height growth MENARCHE Young Adult 03 medical and health sciences AGE SDG 3 - Good Health and Well-being Prepuberty Internal medicine Genetics medicine /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_Humans Molecular Biology 030304 developmental biology Sign Menarche FACTOR RECEPTOR-3 MUTATIONS pubertal timing Puberty ta3121 medicine.disease Obesity Body Height Genetic architecture Endocrinology POPULATION COHORT gene expression Body mass index Follow-Up Studies Genome-Wide Association Study

description

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P<1.67x1028) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits. Refereed/Peer-reviewed

year	journal	country	edition	language
2013-07-01

10.1093/hmg/ddt104 https://hdl.handle.net/1959.8/152978