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Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. / Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Bojesen, Stig E; Nordestgaard, Børge G; PRACTICAL Consortium.
I:
Nature Genetics, Bind 47, Nr. 11, 11.2015, s. 1294-303 + 2 unpag.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
Day, FR, Ruth, KS, Thompson, DJ, Lunetta, KL, Pervjakova, N, Chasman, DI, Stolk, L, Finucane, HK, Sulem, P, Bulik-Sullivan, B, Esko, T, Johnson, AD, Elks, CE, Franceschini, N, He, C, Altmaier, E, Brody, JA, Franke, LL, Huffman, JE, Keller, MF, McArdle, PF, Nutile, T, Porcu, E, Robino, A, Rose, LM, Schick, UM, Smith, JA, Teumer, A, Traglia, M, Vuckovic, D, Yao, J, Zhao, W, Albrecht, E, Amin, N, Corre, T, Hottenga, J-J, Mangino, M, Smith, AV, Tanaka, T, Abecasis, GR, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Arnold, AM, Barbieri, C, Beckmann, MW, Beeghly-Fadiel, A
, Bojesen, SE, Nordestgaard, BG & PRACTICAL Consortium 2015, '
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair',
Nature Genetics, bind 47, nr. 11, s. 1294-303 + 2 unpag..
https://doi.org/10.1038/ng.3412APA
Day, F. R., Ruth, K. S., Thompson, D. J., Lunetta, K. L., Pervjakova, N., Chasman, D. I., Stolk, L., Finucane, H. K., Sulem, P., Bulik-Sullivan, B., Esko, T., Johnson, A. D., Elks, C. E., Franceschini, N., He, C., Altmaier, E., Brody, J. A., Franke, L. L., Huffman, J. E., ... PRACTICAL Consortium (2015).
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
Nature Genetics,
47(11), 1294-303 + 2 unpag..
https://doi.org/10.1038/ng.3412Vancouver
Day FR, Ruth KS, Thompson DJ, Lunetta KL, Pervjakova N, Chasman DI o.a.
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
Nature Genetics. 2015 nov.;47(11):1294-303 + 2 unpag.
https://doi.org/10.1038/ng.3412Author
Day, Felix R ; Ruth, Katherine S ; Thompson, Deborah J ; Lunetta, Kathryn L ; Pervjakova, Natalia ; Chasman, Daniel I ; Stolk, Lisette ; Finucane, Hilary K ; Sulem, Patrick ; Bulik-Sullivan, Brendan ; Esko, Tõnu ; Johnson, Andrew D ; Elks, Cathy E ; Franceschini, Nora ; He, Chunyan ; Altmaier, Elisabeth ; Brody, Jennifer A ; Franke, Lude L ; Huffman, Jennifer E ; Keller, Margaux F ; McArdle, Patrick F ; Nutile, Teresa ; Porcu, Eleonora ; Robino, Antonietta ; Rose, Lynda M ; Schick, Ursula M ; Smith, Jennifer A ; Teumer, Alexander ; Traglia, Michela ; Vuckovic, Dragana ; Yao, Jie ; Zhao, Wei ; Albrecht, Eva ; Amin, Najaf ; Corre, Tanguy ; Hottenga, Jouke-Jan ; Mangino, Massimo ; Smith, Albert V ; Tanaka, Toshiko ; Abecasis, Gonçalo R ; Andrulis, Irene L ; Anton-Culver, Hoda ; Antoniou, Antonis C ; Arndt, Volker ; Arnold, Alice M ; Barbieri, Caterina ; Beckmann, Matthias W ; Beeghly-Fadiel, Alicia ; Bojesen, Stig E ; Nordestgaard, Børge G ; PRACTICAL Consortium. / Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. I: Nature Genetics. 2015 ; Bind 47, Nr. 11. s. 1294-303 + 2 unpag.
Bibtex
@article{1e4a2af6c8ac4e68b97af417c22088bd,
title = "Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair",
abstract = "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 regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.",
keywords = "Adult, Age Factors, Aging, BRCA1 Protein, Breast Neoplasms, DNA Repair, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genomics, Genotype, Humans, Hypothalamus, Menopause, Middle Aged, Models, Genetic, Phenotype, Reproduction, Signal Transduction",
author = "Day, {Felix R} and Ruth, {Katherine S} and Thompson, {Deborah J} and Lunetta, {Kathryn L} and Natalia Pervjakova and Chasman, {Daniel I} and Lisette Stolk and Finucane, {Hilary K} and Patrick Sulem and Brendan Bulik-Sullivan and T{\~o}nu Esko and Johnson, {Andrew D} and Elks, {Cathy E} and Nora Franceschini and Chunyan He and Elisabeth Altmaier and Brody, {Jennifer A} and Franke, {Lude L} and Huffman, {Jennifer E} and Keller, {Margaux F} and McArdle, {Patrick F} and Teresa Nutile and Eleonora Porcu and Antonietta Robino and Rose, {Lynda M} and Schick, {Ursula M} and Smith, {Jennifer A} and Alexander Teumer and Michela Traglia and Dragana Vuckovic and Jie Yao and Wei Zhao and Eva Albrecht and Najaf Amin and Tanguy Corre and Jouke-Jan Hottenga and Massimo Mangino and Smith, {Albert V} and Toshiko Tanaka and Abecasis, {Gon{\c c}alo R} and Andrulis, {Irene L} and Hoda Anton-Culver and Antoniou, {Antonis C} and Volker Arndt and Arnold, {Alice M} and Caterina Barbieri and Beckmann, {Matthias W} and Alicia Beeghly-Fadiel and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and {PRACTICAL Consortium}",
year = "2015",
month = nov,
doi = "10.1038/ng.3412",
language = "English",
volume = "47",
pages = "1294--303 + 2 unpag.",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "11",
}
RIS
TY - JOUR
T1 - Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair
AU - Day, Felix R
AU - Ruth, Katherine S
AU - Thompson, Deborah J
AU - Lunetta, Kathryn L
AU - Pervjakova, Natalia
AU - Chasman, Daniel I
AU - Stolk, Lisette
AU - Finucane, Hilary K
AU - Sulem, Patrick
AU - Bulik-Sullivan, Brendan
AU - Esko, Tõnu
AU - Johnson, Andrew D
AU - Elks, Cathy E
AU - Franceschini, Nora
AU - He, Chunyan
AU - Altmaier, Elisabeth
AU - Brody, Jennifer A
AU - Franke, Lude L
AU - Huffman, Jennifer E
AU - Keller, Margaux F
AU - McArdle, Patrick F
AU - Nutile, Teresa
AU - Porcu, Eleonora
AU - Robino, Antonietta
AU - Rose, Lynda M
AU - Schick, Ursula M
AU - Smith, Jennifer A
AU - Teumer, Alexander
AU - Traglia, Michela
AU - Vuckovic, Dragana
AU - Yao, Jie
AU - Zhao, Wei
AU - Albrecht, Eva
AU - Amin, Najaf
AU - Corre, Tanguy
AU - Hottenga, Jouke-Jan
AU - Mangino, Massimo
AU - Smith, Albert V
AU - Tanaka, Toshiko
AU - Abecasis, Gonçalo R
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C
AU - Arndt, Volker
AU - Arnold, Alice M
AU - Barbieri, Caterina
AU - Beckmann, Matthias W
AU - Beeghly-Fadiel, Alicia
AU - Bojesen, Stig E
AU - Nordestgaard, Børge G
AU - PRACTICAL Consortium
PY - 2015/11
Y1 - 2015/11
N2 - 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 regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
AB - 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 regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
KW - Adult
KW - Age Factors
KW - Aging
KW - BRCA1 Protein
KW - Breast Neoplasms
KW - DNA Repair
KW - Female
KW - Gene Regulatory Networks
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Genomics
KW - Genotype
KW - Humans
KW - Hypothalamus
KW - Menopause
KW - Middle Aged
KW - Models, Genetic
KW - Phenotype
KW - Reproduction
KW - Signal Transduction
U2 - 10.1038/ng.3412
DO - 10.1038/ng.3412
M3 - Journal article
C2 - 26414677
VL - 47
SP - 1294-303 + 2 unpag.
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -
