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Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

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Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. / Day, Felix R; et al.; Perry, John R B.

In: Nature Genetics, Vol. 49, No. 6, 06.2017, p. 834-841.

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Day, Felix R ; et al. ; Perry, John R B. / Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. In: Nature Genetics. 2017 ; Vol. 49, No. 6. pp. 834-841.

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@article{7d577bcb54bf4c7cbbcfbab3a5390e2e,
title = "Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk",
abstract = "The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000-Genome imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P<5×10-8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4{\%} of the population variance in age at menarche, corresponding to ~25{\%} of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects only when paternally inherited. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support causal links with cancer susceptibility.",
author = "Day, {Felix R} and Nicholas Timpson and {Davey Smith}, George and George McMahon and Lavinia Paternoster and Susan Ring and Debbie Lawlor and {et al.} and Perry, {John R B}",
year = "2017",
month = "6",
doi = "10.1038/ng.3841",
language = "English",
volume = "49",
pages = "834--841",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Springer Nature",
number = "6",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

AU - Day, Felix R

AU - Timpson, Nicholas

AU - Davey Smith, George

AU - McMahon, George

AU - Paternoster, Lavinia

AU - Ring, Susan

AU - Lawlor, Debbie

AU - et al.

AU - Perry, John R B

PY - 2017/6

Y1 - 2017/6

N2 - The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000-Genome imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P<5×10-8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects only when paternally inherited. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support causal links with cancer susceptibility.

AB - The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000-Genome imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P<5×10-8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects only when paternally inherited. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support causal links with cancer susceptibility.

U2 - 10.1038/ng.3841

DO - 10.1038/ng.3841

M3 - Article

C2 - 28436984

VL - 49

SP - 834

EP - 841

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -