ArticlePLoS genetics2009
Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 7 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Genome-wide association study of age at menarche in the Taiwan Biobank suggests NOL4 as a novel associated gene.Journal of human genetics · 2023Pooled it
- Age at menarche and epithelial ovarian cancer risk: A meta-analysis and Mendelian randomization study.Cancer medicine · 2019Pooled it
- Pooled it
- Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies.Scientific reports · 2015Pooled it
- Association of adiposity genetic variants with menarche timing in 92,105 women of European descent.American journal of epidemiology · 2013Pooled it
- Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies.International journal of cancer · 2013Pooled it
- Pooled it
- Trial
- Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.Pharmacogenetics and genomics · 2013Trial
- Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.Psychological medicine · 2012Trial
- Impact of female cigarette smoking on circulating B cells in vivo: the suppressed ICOSLG, TCF3, and VCAM1 gene functional network may inhibit normal cell function.Immunogenetics · 2010Trial
- Genetic determinants of age at menarche: does the LIN28B gene play a role? A narrative review.Hormones (Athens, Greece) · 2025Review
- Association analysis of single nucleotide polymorphisms in the LIFR gene with lambing number in sheep.Frontiers in veterinary science · 2025Article
- A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer.Molecular oncology · 2023Article
- Pituitary Gonadotropin Gene Expression During Induced Onset of Postsmolt Maturation in Male Atlantic Salmon:Frontiers in endocrinology · 2022Article
- MicroRNA-155-5p inhibits the invasion and migration of prostate cancer cells by targeting SPOCK1.Oncology letters · 2020Article
- SPOCK1 Involvement in Epithelial-to-Mesenchymal Transition: A New Target in Cancer Therapy?Cancer management and research · 2020Review
- Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries).Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- Puberty and the Evolution of Developmental Science.Journal of research on adolescence : the official journal of the Society for Research on Adolescence · 2019Review
- Article
Corrections and comments
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Authors and funding
22 authors.
Funding
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 x 10(-3) and 4.37 x 10(-3), respectively, in the Chinese cohort and combined p values (obtained by Fisher's method) of 5.19 x 10(-5) and 1.02 x 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.
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