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PMID: 21102462 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.

Nature genetics ·Vol. 42 ·No. 12 ·2010-12-00 ·Pages 1077-85

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 NM, 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, d'Adamo P, de Faire U, de Geus EJ, Deloukas P, Döring A, Smith GD, Easton DF, Eiriksdottir G, Emilsson V, Eriksson J, Ferrucci L, Folsom AR, Foroud T, Garcia M, Gasparini P, Geller F, Gieger C, GIANT Consortium, 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, Boomsma DI, 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

Abstract

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

MeSH Terms
Adolescent Aging/physiology Body Height/genetics Body Size/genetics Child DNA Copy Number Variations/genetics Female Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Inheritance Patterns/genetics Menarche/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics Reproducibility of Results Time Factors
Authors & Affiliations
175 authors, click to expand affiliations / ORCID
Elks Cathy E
Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Perry John R B
Sulem Patrick
Chasman Daniel I
Franceschini Nora
He Chunyan
Lunetta Kathryn L
Visser Jenny A
Byrne Enda M
Cousminer Diana L
Gudbjartsson Daniel F
Esko Tõnu
Feenstra Bjarke
Hottenga Jouke-Jan
Koller Daniel L
Kutalik Zoltán
Lin Peng
Mangino Massimo
Marongiu Mara
McArdle Patrick F
Smith Albert V
Stolk Lisette
van Wingerden Sophie H
Zhao Jing Hua
Albrecht Eva
Corre Tanguy
Ingelsson Erik
Hayward Caroline
Magnusson Patrik K E
Smith Erin N
Ulivi Shelia
Warrington Nicole M
Zgaga Lina
Alavere Helen
Amin Najaf
Aspelund Thor
Bandinelli Stefania
Barroso Inês
Berenson Gerald S
Bergmann Sven
Blackburn Hannah
Boerwinkle Eric
Buring Julie E
Busonero Fabio
Campbell Harry
Chanock Stephen J
Chen Wei
Cornelis Marilyn C
Couper David
Coviello Andrea D
d'Adamo Pio
de Faire Ulf
de Geus Eco J C
Deloukas Panos
Döring Angela
Smith George Davey
Easton Douglas F
Eiriksdottir Gudny
Emilsson Valur
Eriksson Johan
Ferrucci Luigi
Folsom Aaron R
Foroud Tatiana
Garcia Melissa
Gasparini Paolo
Geller Frank
Gieger Christian
GIANT Consortium
Gudnason Vilmundur
Hall Per
Hankinson Susan E
Ferreli Liana
Heath Andrew C
Hernandez Dena G
Hofman Albert
Hu Frank B
Illig Thomas
Järvelin Marjo-Riitta
Johnson Andrew D
Karasik David
Khaw Kay-Tee
Kiel Douglas P
Kilpeläinen Tuomas O
Kolcic Ivana
Kraft Peter
Launer Lenore J
Laven Joop S E
Li Shengxu
Liu Jianjun
Levy Daniel
Martin Nicholas G
McArdle Wendy L
Melbye Mads
Mooser Vincent
Murray Jeffrey C
Murray Sarah S
Nalls Michael A
Navarro Pau
Nelis Mari
Ness Andrew R
Northstone Kate
Oostra Ben A
Peacock Munro
Palmer Lyle J
Palotie Aarno
Paré Guillaume
Parker Alex N
Pedersen Nancy L
Peltonen Leena
Pennell Craig E
Pharoah Paul
Polasek Ozren
Plump Andrew S
Pouta Anneli
Porcu Eleonora
Rafnar Thorunn
Rice John P
Ring Susan M
Rivadeneira Fernando
Rudan Igor
Sala Cinzia
Salomaa Veikko
Sanna Serena
Schlessinger David
Schork Nicholas J
Scuteri Angelo
Segrè Ayellet V
Shuldiner Alan R
Soranzo Nicole
Sovio Ulla
Srinivasan Sathanur R
Strachan David P
Tammesoo Mar-Liis
Tikkanen Emmi
Toniolo Daniela
Tsui Kim
Tryggvadottir Laufey
Tyrer Jonathon
Uda Manuela
van Dam Rob M
van Meurs Joyce B J
Vollenweider Peter
Waeber Gerard
Wareham Nicholas J
Waterworth Dawn M
Weedon Michael N
Wichmann H Erich
Willemsen Gonneke
Wilson James F
Wright Alan F
Young Lauren
Zhai Guangju
Zhuang Wei Vivian
Bierut Laura J
Boomsma Dorret I
Boyd Heather A
Crisponi Laura
Demerath Ellen W
van Duijn Cornelia M
Econs Michael J
Harris Tamara B
Hunter David J
Loos Ruth J F
Metspalu Andres
Montgomery Grant W
Ridker Paul M
Spector Tim D
Streeten Elizabeth A
Stefansson Kari
Thorsteinsdottir Unnur
Uitterlinden André G
Widen Elisabeth
Murabito Joanne M
Ong Ken K
Murray Anna
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.714
Published
2010-12-00
Pages
1077-85
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3140055
Subset
IM
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NIA NIH HHS · R21 AG032598 · United States
NIDA NIH HHS · R01 DA019963-01A2 · United States
NCI NIH HHS · CA104021 · United States
NIDCR NIH HHS · U01 DE017018 · United States
NHGRI NIH HHS · U01 HG004738 · United States
NHLBI NIH HHS · N01 HC055020 · United States
NIAAA NIH HHS · U10 AA008401 · United States
NICHD NIH HHS · R03 HD061437 · United States
NIAAA NIH HHS · R01 AA013320-05 · United States
NIDA NIH HHS · R01-DA013423 · United States
NIA NIH HHS · R21AG032598 · United States
NHGRI NIH HHS · U01 HG004423 · United States
NIAAA NIH HHS · AA14041 · United States
NIDA NIH HHS · R01 DA019963-03 · United States
NCI NIH HHS · R01 CA040356 · United States
NHGRI NIH HHS · U01 HG004422-01 · United States
NCI NIH HHS · R01 CA063464-10 · United States
NCI NIH HHS · CA089392 · United States
NHLBI NIH HHS · N01-HC-55018 · United States
NHLBI NIH HHS · N01HC55021 · United States
NIDCR NIH HHS · U01 DE018993-01 · United States
NHLBI NIH HHS · R01 HL087641 · United States
NIAAA NIH HHS · R01 AA013326-05 · United States
Cancer Research UK · 10118 · United Kingdom
Medical Research Council · MC_U106188470 · United Kingdom
NICHD NIH HHS · HD-061437 · United States
PHS HHS · RFAHG006033 · United States
NIMHD NIH HHS · 263 MD 9164 · United States
NHGRI NIH HHS · U01 HG004399-02 · United States
NIA NIH HHS · P01 AG025204 · United States
NCI NIH HHS · U01 CA136792 · United States
NHGRI NIH HHS · U01 HG004726-02 · United States
NHLBI NIH HHS · U01 HL069757 · United States
NCI NIH HHS · R37 CA054281 · United States
NHGRI NIH HHS · U01 HG004399 · United States
NIA NIH HHS · N01-AG-5-0002 · United States
NIAAA NIH HHS · AA13326 · United States
Cancer Research UK · A10124 · United Kingdom
NCI NIH HHS · U01 CA136792-03 · United States
NIAMS NIH HHS · R01 AR041398-20 · United States
NCI NIH HHS · CA136792 · United States
NHLBI NIH HHS · N01 HC055016 · United States
Medical Research Council · G9815508 · United Kingdom
NHLBI NIH HHS · R01HL086694 · United States
NHLBI NIH HHS · R01 HL088119 · United States
NCRR NIH HHS · U54RR025204-01 · United States
NHGRI NIH HHS · U01 HG004726 · United States
NIAAA NIH HHS · R01 AA013320 · United States
NIA NIH HHS · P01 AG018397-08 · United States
NHGRI NIH HHS · U01 HG004402-02 · United States
Cancer Research UK · 10124 · United Kingdom
External Links
PubMed source DOI: 10.1038/ng.714 PMC Full Text View journal details
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