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

Details

Serval ID
serval:BIB_A2097124302A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
Journal
Human Molecular Genetics
Author(s)
Cousminer D.L., Berry D.J., Timpson N.J., Ang W., Thiering E., Byrne E.M., Taal H.R., Huikari V., Bradfield J.P., Kerkhof M., Groen-Blokhuis M.M., Kreiner-Møller E., Marinelli M., Holst C., Leinonen J.T., Perry J.R., Surakka I., Pietiläinen O., Kettunen J., Anttila V., Kaakinen M., Sovio U., Pouta A., Das S., Lagou V., Power C., Prokopenko I., Evans D.M., Kemp J.P., St Pourcain B., Ring S., Palotie A., Kajantie E., Osmond C., Lehtimäki T., Viikari J.S., Kähönen M., Warrington N.M., Lye S.J., Palmer L.J., Tiesler C.M., Flexeder C., Montgomery G.W., Medland S.E., Hofman A., Hakonarson H., Guxens M., Bartels M., Salomaa V., Murabito J.M., Murabito J.M., Kaprio J., Sørensen T.I., Ballester F., Bisgaard H., Boomsma D.I., Koppelman G.H., Grant S.F., Jaddoe V.W., Martin N.G., Heinrich J., Pennell C.E., Raitakari O.T., Eriksson J.G., Smith G.D., Hyppönen E., Järvelin M.R., McCarthy M.I., Ripatti S., Widén E.
Working group(s)
ReproGen Consortium, Early Growth Genetics (EGG) Consortium
Contributor(s)
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£££Mònica£££ 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£££Tõnu£££ T. , Feenstra B., Hottenga JJ., Koller DL., Kutalik£££Zoltán£££ 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£££Inês£££ 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., d'Adamo P., 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., Gasparini P., 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.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2013
Volume
22
Number
13
Pages
2735-2747
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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 < 1.67 × 10(-8)) 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.
Keywords
Adiposity/genetics, Adolescent, Age Factors, Body Height/genetics, Body Mass Index, Child, Female, Follow-Up Studies, Gene Expression, Genetic Linkage, Genome-Wide Association Study, Humans, Male, Menarche, Mitogen-Activated Protein Kinase 3/genetics, Mitogen-Activated Protein Kinase 3/metabolism, Neoplasms/genetics, Neoplasms/metabolism, Phenotype, Puberty/genetics, Quantitative Trait Loci, Signal Transduction, Transforming Growth Factor beta/metabolism, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
09/01/2014 16:04
Last modification date
18/01/2021 22:45
Usage data