Napredna pretraga

Pregled bibliografske jedinice broj: 990354

Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT


Day, Felix R.; Ruth, Katherine S.; Thompson, Deborah J.; Knight, Julia A.; Kolcic, Ivana; Polasek, Ozren; Rudan, Igor; Zemunik, Tatijana; Hayward, Caroline; Kardia, Sharon L. R. et al.
Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT // Obstetrical & Gynecological Survey, 70 (2015), 12; 758-762 doi:10.1097/01.ogx.0000473766.71624.99 (međunarodna recenzija, komentar, znanstveni)


Naslov
Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT

Autori
Day, Felix R. ; Ruth, Katherine S. ; Thompson, Deborah J. ; Knight, Julia A. ; Kolcic, Ivana ; Polasek, Ozren ; Rudan, Igor ; Zemunik, Tatijana ; Hayward, Caroline ; Kardia, Sharon L. R. ; Kraft, Peter ; McKnight, Barbara ; Metspalu, Andres ; Morrison, Alanna C. ; Reiner, Alex P. ; Ridker, Paul M. ; Rotter, Jerome I. ; Toniolo, Daniela ; Uitterlinden, André G. ; Ulivi, Sheila ; Völzke, Henry ; Wareham, Nicholas J. ; Weir, David R. ; Yerges- Armstrong, Laura M. ; Price, Alkes L. ; Stefansson, Kari ; Visser, Jenny A. ; Ong, Ken K. ; Chang-Claude, Jenny ; Murabito, Joanne M. ; Perry, John R. B. ; Murray, Anna et al.

Izvornik
Obstetrical & Gynecological Survey (0029-7828) 70 (2015), 12; 758-762

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, komentar, znanstveni

Ključne riječi
GWAS ; meta-analysis ; menopause

Sažetak
Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70, 000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per- year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Ustanove
Medicinski fakultet, Split

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati