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- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 5. |
- Buch, S., et al.
(författare)
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Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- 2023
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41x10(-9), OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94x10(-5), OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12x10(-44)). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
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| 6. |
- Adlarson, Patrik, et al.
(författare)
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Abashian-Booth-Crowe Effect in Basic Double-Pionic Fusion : A New Resonance?
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:24, s. 242302-
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Tidskriftsartikel (refereegranskat)abstract
- We report on an exclusive and kinematically complete high-statistics measurement of the basic double-pionic fusion reaction pn -> d pi(0)pi(0) over the full energy region of the ABC effect, a pronounced low-mass enhancement in the pi pi-invariant mass spectrum. The measurements, which cover also the transition region to the conventional t- channel Delta Delta process, were performed with the upgraded WASA detector setup at COSY. The data reveal the Abashian-Booth-Crowe effect to be uniquely correlated with a Lorentzian energy dependence in the integral cross section. The observables are consistent with a narrow resonance with m = 2.37 GeV, Gamma approximate to 70 MeV and I(J(P)) = 0(3(+)) in both pn and Delta Delta systems. Necessary further tests of the resonance interpretation are discussed.
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| 7. |
- Zheng, TH, et al.
(författare)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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