Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23449627
TITLE
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
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.
DATE PUBLISHED
2013 Jul 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2013/02/27
aheadofprint 2013/03/21
entrez 2013/03/02 06:00
pubmed 2013/03/02 06:00
medline 2014/01/08 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cousminer DL Cousminer Diana L DL Institute for Molecular Medicine, and Department of Public Health, University of Helsinki, Helsinki, Finland.
Berry DJ Berry Diane J DJ
Timpson NJ Timpson Nicholas J NJ
Ang W Ang Wei W
Thiering E Thiering Elisabeth E
Byrne EM Byrne Enda M EM
Taal HR Taal H Rob HR
Huikari V Huikari Ville V
Bradfield JP Bradfield Jonathan P JP
Kerkhof M Kerkhof Marjan M
Groen-Blokhuis MM Groen-Blokhuis Maria M MM
Kreiner-Møller E Kreiner-Møller Eskil E
Marinelli M Marinelli Marcella M
Holst C Holst Claus C
Leinonen JT Leinonen Jaakko T JT
Perry JR Perry John R B JR
Surakka I Surakka Ida I
Pietiläinen O Pietiläinen Olli O
Kettunen J Kettunen Johannes J
Anttila V Anttila Verneri V
Kaakinen M Kaakinen Marika M
Sovio U Sovio Ulla U
Pouta A Pouta Anneli A
Das S Das Shikta S
Lagou V Lagou Vasiliki V
Power C Power Chris C
Prokopenko I Prokopenko Inga I
Evans DM Evans David M DM
Kemp JP Kemp John P JP
St Pourcain B St Pourcain Beate B
Ring S Ring Susan S
Palotie A Palotie Aarno A
Kajantie E Kajantie Eero E
Osmond C Osmond Clive C
Lehtimäki T Lehtimäki Terho T
Viikari JS Viikari Jorma S JS
Kähönen M Kähönen Mika M
Warrington NM Warrington Nicole M NM
Lye SJ Lye Stephen J SJ
Palmer LJ Palmer Lyle J LJ
Tiesler CM Tiesler Carla M T CM
Flexeder C Flexeder Claudia C
Montgomery GW Montgomery Grant W GW
Medland SE Medland Sarah E SE
Hofman A Hofman Albert A
Hakonarson H Hakonarson Hakon H
Guxens M Guxens Mònica M
Bartels M Bartels Meike M
Salomaa V Salomaa Veikko V
ReproGen Consortium
Murabito JM Murabito Joanne M JM
Kaprio J Kaprio Jaakko J
Sørensen TI Sørensen Thorkild I A TI
Ballester F Ballester Ferran F
Bisgaard H Bisgaard Hans H
Boomsma DI Boomsma Dorret I DI
Koppelman GH Koppelman Gerard H GH
Grant SF Grant Struan F A SF
Jaddoe VW Jaddoe Vincent W V VW
Martin NG Martin Nicholas G NG
Heinrich J Heinrich Joachim J
Pennell CE Pennell Craig E CE
Raitakari OT Raitakari Olli T OT
Eriksson JG Eriksson Johan G JG
Smith GD Smith George Davey GD
Hyppönen E Hyppönen Elina E
Järvelin MR Järvelin Marjo-Riitta MR
McCarthy MI McCarthy Mark I MI
Ripatti S Ripatti Samuli S
Widén E Widén Elisabeth E
Early Growth Genetics (EGG) Consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Adair Linda S LS
Ang Wei W
Atalay Mustafa M
van Beijsterveldt Toos T
Bergen Nienke N
Benke Kelly K
Berry Diane J DJ
Boomsma Dorret I DI
Bradfield Jonathan P JP
Charoen Pimphen P
Coin Lachlan L
Cooper Cyrus C
Cousminer Diana L DL
Das Shikta S
Davis Oliver S P OS
Dedoussis George V GV
Elliott Paul P
Estivill Xavier X
Evans David M DM
Feenstra Bjarke B
Flexeder Claudia C
Frayling Tim T
Freathy Rachel M RM
Gaillard Romy R
Geller Frank F
Gillman Matthew M
Grant Struan F A SF
Groen-Blokhuis Maria M
Goh Liang-Kee LK
Guxens Mònica M
Hakonarson Hakon H
Hattersley Andrew T AT
Haworth Claire M A CM
Hadley Dexter D
Hedebrand Johannes J
Heinrich Joachim J
Hinney Anke A
Hirschhorn Joel N JN
Hocher Berthold B
Holloway John W JW
Holst Claus C
Hottenga Jouke Jan JJ
Horikoshi Momoko M
Huikari Ville V
Hypponen Elina E
Iñiguez Carmen C
Jaddoe Vincent W V VW
Jarvelin Marjo-Riitta MR
Kaakinen Marika M
Kilpeläinen Tuomas O TO
Kirin Mirna M
Kowgier Matthew M
Lakka Hanna-Maaria HM
Lakka Timo A TA
Lange Leslie A LA
Lawlor Debbie A DA
Lehtimäki Terho T
Lewin Alex A
Lindgren Cecilia C
Lindi Virpi V
Maggi Reedik R
Marsh Julie J
McCarthy Mark I MI
Melbye Mads M
Middeldorp Christel C
Millwood Iona I
Mohlke Karen L KL
Mook-Kanamori Dennis O DO
Murray Jeffrey C JC
Nivard Michel M
Nohr Ellen Aagaard EA
Ntalla Ioanna I
Oken Emily E
Ong Ken K KK
O'Reilly Paul F PF
Palmer Lyle J LJ
Panoutsopoulou Kalliope K
Pararajasingham Jennifer J
Pearson Ewan R ER
Pennell Craig E CE
Power Chris C
Price Thomas S TS
Prokopenko Inga I
Raitakari Olli T OT
Rodriguez Alina A
Salem Rany M RM
Saw Seang-Mei SM
Scherag Andre A
Sebert Sylvain S
Siitonen Niina N
Simell Olli O
Sørensen Thorkild I A TI
Sovio Ulla U
Pourcain Beate St BS
Strachan David P DP
Sunyer Jordi J
Taal H Rob HR
Teo Yik-Ying YY
Thiering Elisabeth E
Tiesler Carla C
Timpson Nicholas J NJ
Uitterlinden Andre G AG
Valcárcel Beatriz B
Warrington Nicole M NM
White Scott S
Widén Elisabeth E
Willemsen Gonneke G
Wilson James F JF
Yaghootkar Hanieh H
Zeggini Eleftheria E
Elks Cathy E CE
Perry John R B JR
Sulem Patrick P
Chasman Daniel I DI
Franceschini Nora N
He Chunyan C
Lunetta Kathryn L KL
Visser Jenny A JA
Byrne Enda M EM
Cousminer Diana L DL
Gudbjartsson Daniel F DF
Esko Tõnu T
Feenstra Bjarke B
Hottenga Jouke-Jan JJ
Koller Daniel L DL
Kutalik Zoltán Z
Lin Peng P
Mangino Massimo M
Marongiu Mara M
McArdle Patrick F PF
Smith Albert V AV
Stolk Lisette L
van Wingerden Sophie H SH
Zhao Jing Hua JH
Albrecht Eva E
Corre Tanguy T
Ingelsson Erik E
Hayward Caroline C
Magnusson Patrik K E PK
Smith Erin N EN
Ulivi Shelia S
Warrington M M
Zgaga Lina L
Alavere Helen H
Amin Najaf N
Aspelund Thor T
Bandinelli Stefania S
Barroso Inês I
Berenson Gerald S GS
Bergmann Sven S
Blackburn Hannah H
Boerwinkle Eric E
Buring Julie E JE
Busonero Fabio F
Campbell Harry H
Chanock Stephen J SJ
Chen Wei W
Cornelis Marilyn C MC
Couper David D
Coviello Andrea D AD
d'Adamo Pio P
de Faire Ulf U
de Geus Eco J C EJ
Deloukas Panos P
Döring Angela A
Davey Smith George G
Easton Douglas F DF
Eiriksdottir Gudny G
Emilsson Valur V
Eriksson Johan J
Ferrucci Luigi L
Folsom Aaron R AR
Foroud Tatiana T
Garcia Melissa M
Gasparini Paolo P
Geller Frank F
Gieger Christian C
Gudnason Vilmundur V
Hall Per P
Hankinson Susan E SE
Ferreli Liana L
Heath Andrew C AC
Hernandez Dena G DG
Hofman Albert A
Hu Frank B FB
Illig Thomas T
Järvelin Marjo-Riitta MR
Johnson Andrew D AD
Karasik David D
Khaw Kay-Tee KT
Kiel Douglas P DP
Kilpeläinen Tuomas O TO
Kolcic Ivana I
Kraft Peter P
Launer Lenore J LJ
Laven Joop S E JS
Li Shengxu S
Liu Jianjun J
Levy Daniel D
Martin Nicholas G NG
McArdle Wendy L WL
Melbye Mads M
Mooser Vincent V
Murray Jeffrey C JC
Murray Sarah S SS
Nalls Michael A MA
Navarro Pau P
Nelis Mari M
Ness Andrew R AR
Northstone Kate K
Oostra Ben A BA
Peacock Munro M
Palmer Lyle J LJ
Palotie Aarno A
Paré Guillaume G
Parker Alex N AN
Pedersen Nancy L NL
Peltonen Leena L
Pennell Craig E CE
Pharoah Paul P
Polasek Ozren O
Plump Andrew S AS
Pouta Anneli A
Porcu Eleonora E
Rafnar Thorunn T
Rice John P JP
Ring Susan M SM
Rivadeneira Fernando F
Rudan Igor I
Sala Cinzia C
Salomaa Veikko V
Sanna Serena S
Schlessinger David D
Schork Nicholas J NJ
Scuteri Angelo A
Segrè Ayellet V AV
Shuldiner Alan R AR
Soranzo Nicole N
Sovio Ulla U
Srinivasan Sathanur R SR
Strachan David P DP
Tammesoo Mar-Liis ML
Tikkanen Emmi E
Toniolo Daniela D
Tsui Kim K
Tryggvadottir Laufey L
Tyrer Jonathon J
Uda Manuela M
van Dam Rob M RM
van Meurs Joyce B J JB
Vollenweider Peter P
Waeber Gerard G
Wareham Nicholas J NJ
Waterworth Dawn M DM
Weedon Michael N MN
Wichmann H Erich HE
Willemsen Gonneke G
Wilson James F JF
Wright Alan F AF
Young Lauren L
Zhai Guangju G
Zhuang Wei Vivian WV
Bierut Laura J LJ
Boyd Heather A HA
Crisponi Laura L
Demerath Ellen W EW
van Duijn Cornelia M CM
Econs Michael J MJ
Harris Tamara B TB
Hunter David J DJ
Loos Ruth J F RJ
Metspalu Andres A
Montgomery Grant W GW
Ridker Paul M PM
Spector Tim D TD
Streeten Elizabeth A EA
Stefansson Kari K
Thorsteinsdottir Unnur U
Uitterlinden André G AG
Widen Elisabeth E
Murabito Joanne M JM
Ong Ken K KK
Murray Anna A
JOURNAL
VOLUME: 22
ISSUE: 13
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2013
MONTH: Jul
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
068545/Z/02 Wellcome Trust United Kingdom
076467 Wellcome Trust United Kingdom
084762MA Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
092731 Wellcome Trust United Kingdom
1RL1MH083268-01 NIMH NIH HHS United States
5R01HL087679-02 NHLBI NIH HHS United States
5R01MH63706:02 NIMH NIH HHS United States
74882 Medical Research Council United Kingdom
AA-08315 NIAAA NIH HHS United States
AA-09203 NIAAA NIH HHS United States
AA-12502 NIAAA NIH HHS United States
G0000934 Medical Research Council United Kingdom
G0500539 Medical Research Council United Kingdom
G0600705 Medical Research Council United Kingdom
G0601653 Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MC_U127592696 Medical Research Council United Kingdom
MC_UP_A620_1014 Medical Research Council United Kingdom
MC_UP_A620_1017 Medical Research Council United Kingdom
MC_UU_12011/1 Medical Research Council United Kingdom
MC_UU_12013/3 Medical Research Council United Kingdom
MOP-82893 Canadian Institutes of Health Research Canada
R01 AG041517 NIA NIH HHS United States
R01 HD056465 NICHD NIH HHS United States
RD1634 Medical Research Council United Kingdom
U01 DK062418 NIDDK NIH HHS United States
U01 HG004423 NHGRI NIH HHS United States
U01 HG006830 NHGRI NIH HHS United States
WT083431MA Wellcome Trust United Kingdom
British Heart Foundation United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adiposity genetics
Adolescent genetics
Age Factors genetics
Body Height genetics
Body Mass Index genetics
Child genetics
Female genetics
Follow-Up Studies genetics
Gene Expression genetics
Genetic Linkage genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Menarche genetics
Mitogen-Activated Protein Kinase 3 metabolism
Neoplasms metabolism
Phenotype metabolism
Puberty genetics
Quantitative Trait Loci genetics
Signal Transduction genetics
Transforming Growth Factor beta metabolism
Young Adult metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Transforming Growth Factor beta
EC 2.7.11.24 Mitogen-Activated Protein Kinase 3
OTHER ID's
OTHERID SOURCE
PMC3674797 NLM