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- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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- Oláh, János, et al.
(författare)
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Lineage sorting by parameres in Limnephilinae subfamily (Trichoptera): with description of a new tribe, new genera and new species
- 2019
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Ingår i: Opuscula Zoologica Instituti Zoosystematici et Oecologici Universitatis Budapestinensis. - 0237-5419 .- 2063-1588. ; 50:S1, s. 3-98
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the new Agaphylax genus with unique paramere organisation has initiated our lineage sorting oftribes by parameres in the Limnephilinae subfamily applying the principles and procedures of fine phenomics in order toestablish transformation series of the polarized plesiomorphy-apomorphy character states for each limnephiline genera.According to the extraordinary high diversity the paramere that is the stimulatory and titillating structure of the phallic organis a speciation supertrait. This adaptive trait is directly involved in the processes of reproductive isolation and diverging assubtle initial split of lineages producing the incipient sibling species in the recent past of contemporary speciation processes.Contrary, the drastic divergence of the Agaphylax plated paramere is much older, similarly to the many-spined parameres ofthe Hesperophylacini tribe. It has been initiated by drastic combined and synchronous external and internal stochastic effects,processed in ancestral sexual integrative adaptation as well as organised and fixed in older and deeper coalescence events andappears as a character with tribe ranking potential. To open a wider perspective, a systemic relational analysis is required inthe future including other adaptive or neutral character transformation series, due to the burden of taxonomic incongruencesgrounded by chimerism in stochastic genetic reticulation. Traits of species are mixed products coming from various sources.Only character combinations can and ought to be analysed in terms how to classify taxa. We have polarized eight genitaliccharacters additional to parameres for a future analysis of the potential of character combinations.Limnephilinae subfamily is composed of Limnephilini, Chilostigmatini, Chaetopterygini, Stenophylacini and Hesperophylacinitribes and here we established the new Agaphylacini tribe. Based on parameres we have delineated taxa in lineagesorting and described two new genera: Fogophylax gen. nov., Simaphylax gen. nov. and fourteen new species: Anaboliaalsoja, A. hepehupa, Asynarchus kimaros, Limnephilus kerekes, L. maghrebensis, L. oblos, Homophylax beges, H. coros,Chaetopteroides plackovicensis, C. rilaensis, Allogamus ketpar, Platyphylax beshkovi, Pycnopsyche letova and P. telea spp.nov. The by-product of this survey is a world atlas of paramere drawings for the entire Limnephilinae subfamily.
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