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Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis

Gallagher, C S ; Mäkinen, N ; Harris, H R ; Rahmioglu, N ; Uimari, O ; Cook, J P ; Shigesi, N ; Ferreira, T ; Velez-Edwards, D R ; Edwards, T L ; Mortlock, S ; Ruhioglu, Z ; Day, F ; Becker, C M ; Karhunen, V ; Martikainen, H ; Järvelin, M-R ; Cantor, R M ; Ridker, P M ; Terry, K L ; Buring, J E ; Gordon, S D ; Medland, S E ; Montgomery, G W ; Nyholt, D R ; Hinds, D A ; Tung, J Y ; Perry, J R B ; Lind, P A ; Painter, J N ; Martin, N G ; Morris, A P ; Chasman, D I ; Missmer, S A ; Zondervan, K T ; Morton, C C

Nature communications, 2019-10, Vol.10 (1), p.4857-11, Article 4857 [Periódico revisado por pares]

England: Nature Publishing Group

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Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis
Autor: Gallagher, C S ; Mäkinen, N ; Harris, H R ; Rahmioglu, N ; Uimari, O ; Cook, J P ; Shigesi, N ; Ferreira, T ; Velez-Edwards, D R ; Edwards, T L ; Mortlock, S ; Ruhioglu, Z ; Day, F ; Becker, C M ; Karhunen, V ; Martikainen, H ; Järvelin, M-R ; Cantor, R M ; Ridker, P M ; Terry, K L ; Buring, J E ; Gordon, S D ; Medland, S E ; Montgomery, G W ; Nyholt, D R ; Hinds, D A ; Tung, J Y ; Perry, J R B ; Lind, P A ; Painter, J N ; Martin, N G ; Morris, A P ; Chasman, D I ; Missmer, S A ; Zondervan, K T ; Morton, C C
Assuntos: Adult ; Ataxia Telangiectasia Mutated Proteins - genetics ; Bleeding ; Chromosome 5 ; Economic analysis ; Endometriosis ; Endometriosis - epidemiology ; Endometriosis - genetics ; Epidemiology ; Female ; Fibroblast growth factor receptor 4 ; Fibroids ; Forkhead Box Protein O1 - genetics ; Forkhead Box Protein O1 - metabolism ; Gene loci ; Genetic analysis ; Genome-Wide Association Study ; Genomes ; Health risks ; Humans ; Hysterectomy ; Leiomyoma - complications ; Leiomyoma - epidemiology ; Leiomyoma - genetics ; Loci ; Mendelian Randomization Analysis ; Menopause ; Menorrhagia - etiology ; Menstruation ; Meta-analysis ; Middle Aged ; Morbidity ; Muscles ; Neoplasms ; Origins ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Receptor, Fibroblast Growth Factor, Type 4 - genetics ; Reproductive system ; Risk analysis ; Signal Transduction ; Smooth muscle ; Telomerase - genetics ; Tumors ; Uterine Neoplasms - complications ; Uterine Neoplasms - epidemiology ; Uterine Neoplasms - genetics ; Uterus ; White People - genetics
É parte de: Nature communications, 2019-10, Vol.10 (1), p.4857-11, Article 4857
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Descrição: Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10 ) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis

England: Nature Publishing Group

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