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

Elks CE, Perry JR, Sulem P et al.

21102462 PubMed ID
GWAS Study Type
102533 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

EC
Elks CE
PJ
Perry JR
SP
Sulem P
CD
Chasman DI
FN
Franceschini N
HC
He C
LK
Lunetta KL
VJ
Visser JA
BE
Byrne EM
CD
Cousminer DL
GD
Gudbjartsson DF
ET
Esko T
FB
Feenstra B
HJ
Hottenga JJ
KD
Koller DL
KZ
Kutalik Z
LP
Lin P
MM
Mangino M
MM
Marongiu M
MP
McArdle PF
SA
Smith AV
SL
Stolk L
VW
van Wingerden SH
ZJ
Zhao JH
AE
Albrecht E
CT
Corre T
IE
Ingelsson E
HC
Hayward C
MP
Magnusson PK
SE
Smith EN
US
Ulivi S
WN
Warrington NM
ZL
Zgaga L
AH
Alavere H
AN
Amin N
AT
Aspelund T
BS
Bandinelli S
BI
Barroso I
BG
Berenson GS
BS
Bergmann S
BH
Blackburn H
BE
Boerwinkle E
BJ
Buring JE
BF
Busonero F
CH
Campbell H
CS
Chanock SJ
CW
Chen W
CM
Cornelis MC
CD
Couper D
CA
Coviello AD
DP
d'Adamo P
DF
de Faire U
DG
de Geus EJ
DP
Deloukas P
DA
Döring A
SG
Smith GD
ED
Easton DF
EG
Eiriksdottir G
EV
Emilsson V
EJ
Eriksson J
FL
Ferrucci L
FA
Folsom AR
FT
Foroud T
GM
Garcia M
GP
Gasparini P
GF
Geller F
GC
Gieger C
GV
Gudnason V
HP
Hall P
HS
Hankinson SE
FL
Ferreli L
HA
Heath AC
HD
Hernandez DG
HA
Hofman A
HF
Hu FB
IT
Illig T
JM
Järvelin MR
JA
Johnson AD
KD
Karasik D
KK
Khaw KT
KD
Kiel DP
KT
Kilpeläinen TO
KI
Kolcic I
KP
Kraft P
LL
Launer LJ
LJ
Laven JS
LS
Li S
LJ
Liu J
LD
Levy D
MN
Martin NG
MW
McArdle WL
MM
Melbye M
MV
Mooser V
MJ
Murray JC
MS
Murray SS
NM
Nalls MA
NP
Navarro P
NM
Nelis M
NA
Ness AR
NK
Northstone K
OB
Oostra BA
PM
Peacock M
PL
Palmer LJ
PA
Palotie A
PG
Paré G
PA
Parker AN
PN
Pedersen NL
PL
Peltonen L
PC
Pennell CE
PP
Pharoah P
PO
Polasek O
PA
Plump AS
PA
Pouta A
PE
Porcu E
RT
Rafnar T
RJ
Rice JP
RS
Ring SM
RF
Rivadeneira F
RI
Rudan I
SC
Sala C
SV
Salomaa V
SS
Sanna S
SD
Schlessinger D
SN
Schork NJ
SA
Scuteri A
SA
Segrè AV
SA
Shuldiner AR
SN
Soranzo N
SU
Sovio U
SS
Srinivasan SR
SD
Strachan DP
TM
Tammesoo ML
TE
Tikkanen E
TD
Toniolo D
TK
Tsui K
TL
Tryggvadottir L
TJ
Tyrer J
UM
Uda M
VD
van Dam RM
VM
van Meurs JB
VP
Vollenweider P
WG
Waeber G
WN
Wareham NJ
WD
Waterworth DM
WM
Weedon MN
WH
Wichmann HE
WG
Willemsen G
WJ
Wilson JF
WA
Wright AF
YL
Young L
ZG
Zhai G
ZW
Zhuang WV
BL
Bierut LJ
BD
Boomsma DI
BH
Boyd HA
CL
Crisponi L
DE
Demerath EW
VD
van Duijn CM
EM
Econs MJ
HT
Harris TB
HD
Hunter DJ
LR
Loos RJ
MA
Metspalu A
MG
Montgomery GW
RP
Ridker PM
ST
Spector TD
SE
Streeten EA
SK
Stefansson K
TU
Thorsteinsdottir U
UA
Uitterlinden AG
WE
Widen E
MJ
Murabito JM
OK
Ong KK
MA
Murray A
Chapter II

Abstract

Summary of the research findings

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.

86,142 European ancestry female individuals, 557 Old Order Amish (founder/genetic isolate) female individuals, 1,103 Erasmus Rucphen (founder/genetic isolate) female individuals

Chapter III

Study Statistics

Key metrics and study information

102533
Total Participants
GWAS
Study Type
Yes
Replicated
Up to 12,813 European ancestry female individuals, 910 Val Borbera (founder/genetic isolate) female individuals, 348 Orcadian (founder/genetic isolate) female individuals, 338 Friuli Venezia Giulia (founder/genetic isolate) female individuals, 322 Carlantino (founder/genetic/isolate) female individuals
Replication Participants
European
Ancestry
Sweden, U.S., Australia, Italy, Germany, U.K., Croatia, Finland, Iceland, Netherlands, Switzerland
Recruitment Country
Chapter IV

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