Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.
Nat Genet
; 49(6): 834-841, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28436984
ABSTRACT
The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to â¼370,000 women, we identify 389 independent signals (P < 5 × 10-8) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain â¼7.4% of the population variance in age at menarche, corresponding to â¼25% of the estimated heritability. We implicate â¼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleoproteínas
/
Menarca
/
Puberdade
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Proteínas de Membrana
/
Neoplasias
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Female
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Humans
/
Male
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido