Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche

Yao Zhong Liu, Yan Fang Guo, Liang Wang, Li Jun Tan, Xiao Gang Liu, Yu Fang Pei, Han Yan, Dong Hai Xiong, Fei Yan Deng, Na Yu, Yin Ping Zhang, Lei Zhang, Shu Feng Lei, Xiang Ding Chen, Hong Bin Liu, Xue Zhen Zhu, Shawn Levy, Christopher J. Papasian, Betty M. Drees, James J. HamiltonRobert R. Recker, Hong Wen Deng

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

For females, menarche is a most significant physiological event. Age at menarche (AAM) is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS) examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects-all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan), which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR) q-3 and 4.37 ×10-3, respectively, in the Chinese cohort and combined p values (obtained by Fisher's method) of 5.19×10-5 and 1.02×10-4, respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2), a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM. Copyright:

Original languageEnglish (US)
JournalPLoS genetics
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2009

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Fingerprint Dive into the research topics of 'Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche'. Together they form a unique fingerprint.

  • Cite this

    Liu, Y. Z., Guo, Y. F., Wang, L., Tan, L. J., Liu, X. G., Pei, Y. F., Yan, H., Xiong, D. H., Deng, F. Y., Yu, N., Zhang, Y. P., Zhang, L., Lei, S. F., Chen, X. D., Liu, H. B., Zhu, X. Z., Levy, S., Papasian, C. J., Drees, B. M., ... Deng, H. W. (2009). Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche. PLoS genetics, 5(3). https://doi.org/10.1371/journal.pgen.1000420