Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1000420
Title: Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche
Authors: 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.
Hamilton J.J.
Recker R.R.
Deng H.-W.
Keywords: gelatinase A
kazal like domain proteoglycan
membrane protein
osteonectin
protein cwcv
proteoglycan
unclassified drug
proteoglycan
SPOCK1 protein, human
adult
aged
article
controlled study
enzyme activation
female
gene
gene identification
gene replication
genetic association
genetic variability
genome analysis
haplotype
human
menarche
menstruation
single nucleotide polymorphism
spock gene
age
aging
Caucasian
genetic association
genetics
middle aged
Adult
Age Factors
Aging
European Continental Ancestry Group
Female
Genome-Wide Association Study
Humans
Menarche
Middle Aged
Polymorphism, Single Nucleotide
Proteoglycans
Issue Date: 2009
Citation: 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., Hamilton J.J., Recker R.R., Deng H.-W. (2009). Genome-Wide association analyses identify SPOCKas a key novel gene underlying age at menarche. PLoS Genetics 5 (3). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1000420
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<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09×10 -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: © 2009 Liu et al.
Source Title: PLoS Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/161677
ISSN: 15537390
DOI: 10.1371/journal.pgen.1000420
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