Meta-analysis of loci associated with age at natural menopause in African-American women.
Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA ctchen@fhcrc.org rajkovic@upmc.edu murabito@bu.edu christopher.haiman@med.usc.edu.
Christina T L
CT
Chen
Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
Ching-Ti
CT
Liu
Department of Preventive Medicine.
Gary K
GK
Chen
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Jeanette S
JS
Andrews
Department of Biostatistics.
Alice M
AM
Arnold
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
Jill
J
Dreyfus
Department of Epidemiology, Gillings School of Global Public Health.
Nora
N
Franceschini
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD 20814, USA.
Melissa E
ME
Garcia
Department of Biostatistics.
Kathleen F
KF
Kerr
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Guo
G
Li
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Kurt K
KK
Lohman
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Solomon K
SK
Musani
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Michael A
MA
Nalls
Department of Pediatrics and Biomedical Sciences.
Leslie J
LJ
Raffel
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
Jennifer
J
Smith
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Christine B
CB
Ambrosone
The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
Elisa V
EV
Bandera
Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Leslie
L
Bernstein
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Angela
A
Britton
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Robert G
RG
Brzyski
Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anne
A
Cappola
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Christopher S
CS
Carlson
Department of Biostatistics, Gillings School of Global Public Health.
David
D
Couper
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Sandra L
SL
Deming
Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Mark O
MO
Goodarzi
Department of Epidemiology, Gillings School of Global Public Health.
Gerardo
G
Heiss
Division of Epidemiology, Department of Health Research & Policy, Stanford University School of Medicine, Stanford, CA 94305, USA.
Esther M
EM
John
Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA Division of Clinical Informatics, Beth Israel Deaconess Medical Center, Boston, MA 02118, USA.
Xiaoning
X
Lu
Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, HI 96813, USA.
Loic
L
Le Marchand
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Kristin
K
Marciante
Department of Biostatistics.
Barbara
B
Mcknight
Department of Epidemiology, Gillings School of Global Public Health Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
Robert
R
Millikan
Department of Epidemiology and Biostatistics, Case Western University, Cleveland, OH 44106, USA.
Nora L
NL
Nock
Department of Epidemiology, Gillings School of Global Public Health Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
Andrew F
AF
Olshan
Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Michael F
MF
Press
Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Dhananjay
D
Vaiyda
Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA 98109, USA.
Nancy F
NF
Woods
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Herman A
HA
Taylor
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
Wei
W
Zhao
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Wei
W
Zheng
Health Disparities Research Section, Clinical Research Branch.
Michele K
MK
Evans
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD 20814, USA.
Tamara B
TB
Harris
Department of Preventive Medicine.
Brian E
BE
Henderson
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
Sharon L R
SL
Kardia
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Charles
C
Kooperberg
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Yongmei
Y
Liu
Division of Geriatric Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Thomas H
TH
Mosley
Departments of Medicine, Epidemiology and Health Services, University of Washington and Group Health Research Institute, Seattle, WA, USA.
Bruce
B
Psaty
School of Medicine, Vanderbilt University, Nashville, TN 37240, USA.
Melissa
M
Wellons
Division of Geriatric Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Beverly G
BG
Windham
Laboratory of Personality and Cognition, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Alan B
AB
Zonderman
Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
L Adrienne
LA
Cupples
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
Ellen W
EW
Demerath
Department of Preventive Medicine ctchen@fhcrc.org rajkovic@upmc.edu murabito@bu.edu christopher.haiman@med.usc.edu.
Christopher
C
Haiman
National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston, MA, USA ctchen@fhcrc.org rajkovic@upmc.edu murabito@bu.edu christopher.haiman@med.usc.edu.
Joanne M
JM
Murabito
Department of Obstetrics, Gynecology and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA ctchen@fhcrc.org rajkovic@upmc.edu murabito@bu.edu christopher.haiman@med.usc.edu.
Aleksandar
A
Rajkovic
D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D002877:Chromosomes, Human; D005260:Female; D056426:Genetic Loci; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008593:Menopause / Q000208:ethnology* / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*