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
22267201
TITLE
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.
ABSTRACT
To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
DATE PUBLISHED
2012 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/07/21
accepted 2011/12/02
aheadofprint 2012/01/22
entrez 2012/01/24 06:00
pubmed 2012/01/24 06:00
medline 2012/04/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Stolk L Stolk Lisette L Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Perry JR Perry John R B JR
Chasman DI Chasman Daniel I DI
He C He Chunyan C
Mangino M Mangino Massimo M
Sulem P Sulem Patrick P
Barbalic M Barbalic Maja M
Broer L Broer Linda L
Byrne EM Byrne Enda M EM
Ernst F Ernst Florian F
Esko T Esko Tõnu T
Franceschini N Franceschini Nora N
Gudbjartsson DF Gudbjartsson Daniel F DF
Hottenga JJ Hottenga Jouke-Jan JJ
Kraft P Kraft Peter P
McArdle PF McArdle Patrick F PF
Porcu E Porcu Eleonora E
Shin SY Shin So-Youn SY
Smith AV Smith Albert V AV
van Wingerden S van Wingerden Sophie S
Zhai G Zhai Guangju G
Zhuang WV Zhuang Wei V WV
Albrecht E Albrecht Eva E
Alizadeh BZ Alizadeh Behrooz Z BZ
Aspelund T Aspelund Thor T
Bandinelli S Bandinelli Stefania S
Lauc LB Lauc Lovorka Barac LB
Beckmann JS Beckmann Jacques S JS
Boban M Boban Mladen M
Boerwinkle E Boerwinkle Eric E
Broekmans FJ Broekmans Frank J FJ
Burri A Burri Andrea A
Campbell H Campbell Harry H
Chanock SJ Chanock Stephen J SJ
Chen C Chen Constance C
Cornelis MC Cornelis Marilyn C MC
Corre T Corre Tanguy T
Coviello AD Coviello Andrea D AD
d'Adamo P d'Adamo Pio P
Davies G Davies Gail G
de Faire U de Faire Ulf U
de Geus EJ de Geus Eco J C EJ
Deary IJ Deary Ian J IJ
Dedoussis GV Dedoussis George V Z GV
Deloukas P Deloukas Panagiotis P
Ebrahim S Ebrahim Shah S
Eiriksdottir G Eiriksdottir Gudny G
Emilsson V Emilsson Valur V
Eriksson JG Eriksson Johan G JG
Fauser BC Fauser Bart C J M BC
Ferreli L Ferreli Liana L
Ferrucci L Ferrucci Luigi L
Fischer K Fischer Krista K
Folsom AR Folsom Aaron R AR
Garcia ME Garcia Melissa E ME
Gasparini P Gasparini Paolo P
Gieger C Gieger Christian C
Glazer N Glazer Nicole N
Grobbee DE Grobbee Diederick E DE
Hall P Hall Per P
Haller T Haller Toomas T
Hankinson SE Hankinson Susan E SE
Hass M Hass Merli M
Hayward C Hayward Caroline C
Heath AC Heath Andrew C AC
Hofman A Hofman Albert A
Ingelsson E Ingelsson Erik E
Janssens AC Janssens A Cecile J W AC
Johnson AD Johnson Andrew D AD
Karasik D Karasik David D
Kardia SL Kardia Sharon L R SL
Keyzer J Keyzer Jules J
Kiel DP Kiel Douglas P DP
Kolcic I Kolcic Ivana I
Kutalik Z Kutalik Zoltán Z
Lahti J Lahti Jari J
Lai S Lai Sandra S
Laisk T Laisk Triin T
Laven JS Laven Joop S E JS
Lawlor DA Lawlor Debbie A DA
Liu J Liu Jianjun J
Lopez LM Lopez Lorna M LM
Louwers YV Louwers Yvonne V YV
Magnusson PK Magnusson Patrik K E PK
Marongiu M Marongiu Mara M
Martin NG Martin Nicholas G NG
Klaric IM Klaric Irena Martinovic IM
Masciullo C Masciullo Corrado C
McKnight B McKnight Barbara B
Medland SE Medland Sarah E SE
Melzer D Melzer David D
Mooser V Mooser Vincent V
Navarro P Navarro Pau P
Newman AB Newman Anne B AB
Nyholt DR Nyholt Dale R DR
Onland-Moret NC Onland-Moret N Charlotte NC
Palotie A Palotie Aarno A
Paré G Paré Guillaume G
Parker AN Parker Alex N AN
Pedersen NL Pedersen Nancy L NL
Peeters PH Peeters Petra H M PH
Pistis G Pistis Giorgio G
Plump AS Plump Andrew S AS
Polasek O Polasek Ozren O
Pop VJ Pop Victor J M VJ
Psaty BM Psaty Bruce M BM
Räikkönen K Räikkönen Katri K
Rehnberg E Rehnberg Emil E
Rotter JI Rotter Jerome I JI
Rudan I Rudan Igor I
Sala C Sala Cinzia C
Salumets A Salumets Andres A
Scuteri A Scuteri Angelo A
Singleton A Singleton Andrew A
Smith JA Smith Jennifer A JA
Snieder H Snieder Harold H
Soranzo N Soranzo Nicole N
Stacey SN Stacey Simon N SN
Starr JM Starr John M JM
Stathopoulou MG Stathopoulou Maria G MG
Stirrups K Stirrups Kathleen K
Stolk RP Stolk Ronald P RP
Styrkarsdottir U Styrkarsdottir Unnur U
Sun YV Sun Yan V YV
Tenesa A Tenesa Albert A
Thorand B Thorand Barbara B
Toniolo D Toniolo Daniela D
Tryggvadottir L Tryggvadottir Laufey L
Tsui K Tsui Kim K
Ulivi S Ulivi Sheila S
van Dam RM van Dam Rob M RM
van der Schouw YT van der Schouw Yvonne T YT
van Gils CH van Gils Carla H CH
van Nierop P van Nierop Peter P
Vink JM Vink Jacqueline M JM
Visscher PM Visscher Peter M PM
Voorhuis M Voorhuis Marlies M
Waeber G Waeber Gérard G
Wallaschofski H Wallaschofski Henri H
Wichmann HE Wichmann H Erich HE
Widen E Widen Elisabeth E
Wijnands-van Gent CJ Wijnands-van Gent Colette J M CJ
Willemsen G Willemsen Gonneke G
Wilson JF Wilson James F JF
Wolffenbuttel BH Wolffenbuttel Bruce H R BH
Wright AF Wright Alan F AF
Yerges-Armstrong LM Yerges-Armstrong Laura M LM
Zemunik T Zemunik Tatijana T
Zgaga L Zgaga Lina L
Zillikens MC Zillikens M Carola MC
Zygmunt M Zygmunt Marek M
LifeLines Cohort Study
Arnold AM Arnold Alice M AM
Boomsma DI Boomsma Dorret I DI
Buring JE Buring Julie E JE
Crisponi L Crisponi Laura L
Demerath EW Demerath Ellen W EW
Gudnason V Gudnason Vilmundur V
Harris TB Harris Tamara B TB
Hu FB Hu Frank B FB
Hunter DJ Hunter David J DJ
Launer LJ Launer Lenore J LJ
Metspalu A Metspalu Andres A
Montgomery GW Montgomery Grant W GW
Oostra BA Oostra Ben A BA
Ridker PM Ridker Paul M PM
Sanna S Sanna Serena S
Schlessinger D Schlessinger David D
Spector TD Spector Tim D TD
Stefansson K Stefansson Kari K
Streeten EA Streeten Elizabeth A EA
Thorsteinsdottir U Thorsteinsdottir Unnur U
Uda M Uda Manuela M
Uitterlinden AG Uitterlinden André G AG
van Duijn CM van Duijn Cornelia M CM
Völzke H Völzke Henry H
Murray A Murray Anna A
Murabito JM Murabito Joanne M JM
Visser JA Visser Jenny A JA
Lunetta KL Lunetta Kathryn L KL
INVESTIGATORS
JOURNAL
VOLUME: 44
ISSUE: 3
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2012
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
263 MD821336 NIMHD NIH HHS United States
263 MD9164 13 NIMHD NIH HHS United States
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/710 Chief Scientist Office United Kingdom
G0600705 Medical Research Council United Kingdom
G0700704 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U127561128 Medical Research Council United Kingdom
MC_U127592696 Medical Research Council United Kingdom
N01 AG012100 NIA NIH HHS United States
N01 AG012109 NIA NIH HHS United States
N01 AG050002 NIA NIH HHS United States
N01 HC025195 NHLBI NIH HHS United States
N01 HC035129 NHLBI NIH HHS United States
N01 HC055015 NHLBI NIH HHS United States
N01 HC085086 NHLBI NIH HHS United States
N02 HL64278 NHLBI NIH HHS United States
P01 CA087969 NCI NIH HHS United States
P01 CA087969-12 NCI NIH HHS United States
P30 DK063491 NIDDK NIH HHS United States
P30 DK072488 NIDDK NIH HHS United States
R01 AR041398 NIAMS NIH HHS United States
R01 AR041398-09 NIAMS NIH HHS United States
R01 CA040356-15 NCI NIH HHS United States
R01 CA047988 NCI NIH HHS United States
R01 CA047988-09 NCI NIH HHS United States
R01 HL043851 NHLBI NIH HHS United States
R01 HL043851-09 NHLBI NIH HHS United States
R01 HL087660 NHLBI NIH HHS United States
R01 HL087660-01 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01 HL105756-01 NHLBI NIH HHS United States
R21 AG032598 NIA NIH HHS United States
R21 AG032598-01 NIA NIH HHS United States
R69/0208 The Dunhill Medical Trust United Kingdom
U01 CA098233 NCI NIH HHS United States
U01 CA098233-01 NCI NIH HHS United States
U01 HG004402 NHGRI NIH HHS United States
U01 HG004402-01 NHGRI NIH HHS United States
U01 HL072515 NHLBI NIH HHS United States
U01 HL072515-01 NHLBI NIH HHS United States
U01 HL084756 NHLBI NIH HHS United States
U01 HL084756-01 NHLBI NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Age Factors
DNA Helicases genetics
DNA Primase genetics
DNA Repair genetics
DNA Repair Enzymes genetics
DNA-Directed DNA Polymerase genetics
European Continental Ancestry Group genetics
Exodeoxyribonucleases genetics
Female genetics
Genetic Loci genetics
Genome-Wide Association Study genetics
Humans genetics
Immunity genetics
Menopause physiology
Polymorphism, Single Nucleotide genetics
Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Proteins
147155-45-1 PRRC2A protein, human
EC 2.7.7.- DNA Primase
EC 2.7.7.- POLG protein, human
EC 2.7.7.7 DNA-Directed DNA Polymerase
EC 3.1.- EXO1 protein, human
EC 3.1.- Exodeoxyribonucleases
EC 3.6.4.- DNA Helicases
EC 5.99.- HEL308 protein, human
EC 6.5.1.- DNA Repair Enzymes
OTHER ID's
OTHERID SOURCE
NIHMS342040 NLM
PMC3288642 NLM