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Hum Mol Genet. 2014 Jun 15;23(12):3327-42. doi: 10.1093/hmg/ddu041. Epub 2014 Feb 2.

Meta-analysis of loci associated with age at natural menopause in African-American women.

Author information

1
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.
2
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.
3
Department of Preventive Medicine.
4
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
5
Department of Biostatistics.
6
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
7
Department of Epidemiology, Gillings School of Global Public Health.
8
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD 20814, USA.
9
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
10
University of Mississippi Medical Center, Jackson, MS 39216, USA.
11
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
12
Department of Pediatrics and Biomedical Sciences.
13
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
14
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
15
The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
16
Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
17
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
18
Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
19
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
20
Department of Biostatistics, Gillings School of Global Public Health.
21
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
22
Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
23
Division of Epidemiology, Department of Health Research & Policy, Stanford University School of Medicine, Stanford, CA 94305, USA.
24
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.
25
Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, HI 96813, USA.
26
Department of Epidemiology, Gillings School of Global Public Health Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
27
Department of Epidemiology and Biostatistics, Case Western University, Cleveland, OH 44106, USA.
28
Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
29
Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
30
Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA 98109, USA.
31
Health Disparities Research Section, Clinical Research Branch.
32
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
33
Division of Geriatric Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
34
Departments of Medicine, Epidemiology and Health Services, University of Washington and Group Health Research Institute, Seattle, WA, USA.
35
School of Medicine, Vanderbilt University, Nashville, TN 37240, USA.
36
Laboratory of Personality and Cognition, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
37
Department of Preventive Medicine ctchen@fhcrc.org rajkovic@upmc.edu murabito@bu.edu christopher.haiman@med.usc.edu.
38
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.
39
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.

Abstract

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.

PMID:
24493794
PMCID:
PMC4030781
DOI:
10.1093/hmg/ddu041
[Indexed for MEDLINE]
Free PMC Article

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