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. Hamilton & 2 others Robert R. Recker, Hong Wen Deng

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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
JournalPLoS Genetics
Volume5
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

menarche
Menarche
Genome-Wide Association Study
genome
gene
Genes
genes
Single Nucleotide Polymorphism
Osteonectin
gelatinase A
proteoglycans
Age Factors
Matrix Metalloproteinase 2
Proteoglycans
hemorrhage
Siblings
matrix
Genome
Hemorrhage
genome-wide association study

All Science Journal Classification (ASJC) codes

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

Cite this

Liu, Y. Z., Guo, Y. F., Wang, L., Tan, L. J., Liu, X. G., Pei, Y. F., ... 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

Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche. / Liu, Yao Zhong; Guo, Yan Fang; Wang, Liang; Tan, Li Jun; Liu, Xiao Gang; Pei, Yu Fang; Yan, Han; Xiong, Dong Hai; Deng, Fei Yan; Yu, Na; Zhang, Yin Ping; Zhang, Lei; Lei, Shu Feng; Chen, Xiang Ding; Liu, Hong Bin; Zhu, Xue Zhen; Levy, Shawn; Papasian, Christopher J.; Drees, Betty M.; Hamilton, James J.; Recker, Robert R.; Deng, Hong Wen.

In: PLoS Genetics, Vol. 5, No. 3, 03.2009.

Research output: Contribution to journalArticle

Liu, YZ, Guo, YF, Wang, L, Tan, LJ, Liu, XG, Pei, YF, Yan, H, Xiong, DH, Deng, FY, Yu, N, Zhang, YP, Zhang, L, Lei, SF, Chen, XD, Liu, HB, Zhu, XZ, Levy, S, Papasian, CJ, Drees, BM, Hamilton, JJ, Recker, RR & Deng, HW 2009, 'Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche', PLoS Genetics, vol. 5, no. 3. https://doi.org/10.1371/journal.pgen.1000420
Liu, Yao Zhong ; Guo, Yan Fang ; Wang, Liang ; Tan, Li Jun ; Liu, Xiao Gang ; Pei, Yu Fang ; Yan, Han ; Xiong, Dong Hai ; Deng, Fei Yan ; Yu, Na ; Zhang, Yin Ping ; Zhang, Lei ; Lei, Shu Feng ; Chen, Xiang Ding ; Liu, Hong Bin ; Zhu, Xue Zhen ; Levy, Shawn ; Papasian, Christopher J. ; Drees, Betty M. ; Hamilton, James J. ; Recker, Robert R. ; Deng, Hong Wen. / Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche. In: PLoS Genetics. 2009 ; Vol. 5, No. 3.
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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:",
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AU - Zhu, Xue Zhen

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