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

Christina T L Chen, Ching Ti Liu, Gary K. Chen, Jeanette S. Andrews, Alice M. Arnold, Jill Dreyfus, Nora Franceschini, Melissa E. Garcia, Kathleen F. Kerr, Guo Li, Kurt K. Lohman, Solomon K. Musani, Michael A. Nalls, Leslie J. Raffel, Jennifer Smith, Christine B. Ambrosone, Elisa V. Bandera, Leslie Bernstein, Angela Britton, Robert G. BrzyskiAnne Cappola, Christopher S. Carlson, David Couper, Sandra L. Deming, Mark O. Goodarzi, Gerardo Heiss, Esther M. John, Xiaoning Lu, Loic Le Marchand, Kristin Marciante, Barbara Mcknight, Robert Millikan, Nora L. Nock, Andrew F. Olshan, Michael F. Press, Dhananjay Vaiyda, Nancy F. Woods, Herman A. Taylor, Wei Zhao, Wei Zheng, Michele K. Evans, Tamara B. Harris, Brian E. Henderson, Sharon L R Kardia, Charles Kooperberg, Yongmei Liu, Thomas H. Mosley, Bruce Psaty, Melissa Wellons, Beverly G. Windham, Alan B. Zonderman, L. Adrienne Cupples, Ellen W. Demerath, Christopher Haiman, Joanne M. Murabito, Aleksandar Rajkovic

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Age atmenopause 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 men opause. 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 Africanancestry derivedfrom 11studies across the USA.We did not identify any additional loci significantly associated with age at men opause in African Americans.We replicated the associations between six lociandage at men opause (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.

Original languageEnglish (US)
Pages (from-to)3327-3342
Number of pages16
JournalHuman molecular genetics
Issue number12
StatePublished - Jun 15 2014

Bibliographical note

Funding Information:
The Cardiovascular Health Study was supported by contracts HHSN268201200036C, N01-HC-85239, N01 HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85086 and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG-023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center and Cedars-Sinai Board of Governors’ Chair in Medical Genetics (JIR).

Funding Information:
The Health ABC Study was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C.

Funding Information:
The Genetic Epidemiology Network of Arteriopathy (GENOA) phenotyping and genome-wide genotyping was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL54457 and HL087660). Geno-typing was performed at the Mayo Clinic (Stephen T. Turner, Mariza de Andrade, Julie Cunningham) and was made possible by the University of Texas Health Sciences Center (Eric Boer-winkle, Megan L. Grove-Gaona). We thank the families that participated in the GENOA study.

Funding Information:
The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This manuscript was prepared in collaboration with investigators of the WHI, and has been approved by the WHI. WHI investigators are listed at WHI_investigators_shortlist.pdf.

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268 201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

Funding Information:
The National Institute of Health funded the CARe Consortium that contributed data and DNA to the Broad Institute (N01-HC-65226) to create the phenotype/genotype resource for wide dissemination to the biomedical community. NIH contract HHSN268200900055C and subcontract 5215810-550000234, provided statistical resources for the age at menopause genetic association analyses conducted in the CARe cohorts with additional support from R21AG032598.

Funding Information:
The MESA and MESA Family are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159 through N01-HC-95169 and CTSA UL1-RR-024156. Funding for MESA Family is provided by grants R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, UL1-RR-025005, by the National Center for Research Resources, Grant UL1RR033176, and is now at the National Center for Advancing Translational Sciences, Grant UL1TR000124. Funding for genotyping was provided by NHLBI Contract N02-HL-6-4278 and N01-HC-65226.

Funding Information:
The African American Breast Cancer Consortium was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to C.A.H. (W81XWH-08-1-0383) and the Norris Foundation. Each of the participating studies was supported by the following grants: MEC (National Institutes of Health grants R01-CA63464 and R37-CA54281) and CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, National Institutes of Health, grant number P30-ES10126) .

Funding Information:
The Jackson Heart Study was supported by National Institutes of Health contracts (N01-HC-95170, N01-HC-95171 and N01-HC-95172) provided by the National Heart, Lung, and Blood Institute and the National Center for Minority Health and Health Disparities (NCMHD).

Funding Information:
The HANDLS study was supported by the Intramural Research Program of the NIH, National Institute on Aging and the National Center on Minority Health and Health Disparities (contract # Z01-AG000513 and human subjects protocol # 2009-149). Data analyses for the HANDLS study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (


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