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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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- Ablikim, M., et al.
(författare)
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First measurement of e(+)e(-) -> pK(S)(0)(n)over-barK(-) + c.c. above open charm threshold
- 2018
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 98:3
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Tidskriftsartikel (refereegranskat)abstract
- The process e(+)e(-) -> pK(S)(0)(n) over barK(-) + c.c. and its intermediate processes are studied for the first time, using data samples collected with the BESIII detector at BEPCII at center-of-mass energies of 3.773, 4.008, 4.226, 4.258, 4.358, 4.416, and 4.600 GeV, with a total integrated luminosity of 7.4 fb(-1). The Born cross section of e(+)e(-) -> pK(S)(0)(n) over barK(-) + c.c. is measured at each center-of-mass energy, but no significant resonant structure in the measured cross-section line shape between 3.773 and 4.600 GeV is observed. No evident structure is detected in the pK(-), nK(S)(0), pK(S)(0), nK(+), p (n) over bar, or (KSK-)-K-0 invariant mass distributions except for Lambda(1520). The Born cross sections of e(+)e(-) -> Lambda(1520)(n) over barK(S)(0) + c.c. and e(+)e(-) -> Lambda(1520)(p) over barK(+) + c.c. are measured, and the 90% confidence level upper limits on the Born cross sections of e(+)e(-) -> Lambda(1520)(Lambda) over bar (1520) are determined at the seven center-of-mass energies. There is an evident difference in line shape and magnitude of the measured cross sections between e(+)e(-) -> Lambda(1520)(-> pK(-))(n) over barK(S)(0) and e(+)e(-) -> pK-(Lambda) over bar (1520)(-> (n) over barK(S)(0)).
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| 6. |
- Ablikim, M., et al.
(författare)
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Measurement of e(+)e(-) -> D(D)over-bar cross sections at the psi(3770) resonance
- 2018
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Ingår i: Chinese Physics C. - : IOP PUBLISHING LTD. - 1674-1137 .- 2058-6132. ; 42:8
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Tidskriftsartikel (refereegranskat)abstract
- We report new measurements of the cross sections for the production of D (D) over bar final states at the psi(3770) resonance. Our data sample consists of an integrated luminosity of 2.93 fb(-1) of e(+)e(-) annihilation data produced by the BEPCII collider and collected and analyzed with the BESIII detector. We exclusively reconstruct three D-0 and six D+ hadronic decay modes and use the ratio of the yield of fully reconstructed D (D) over bar events ("double tags") to the yield of all reconstructed D or (D) over bar mesons ("single tags") to determine the number of D-0(D) over bar (0) and D+D- events, benefiting from the cancellation of many systematic uncertainties. Combining these yields with an independent determination of the integrated luminosity of the data sample, we find the cross sections to be sigma(e(+)e(-) -> D-0(D) over bar (0)(-) )=(3.615 +/- 0.010 +/- 0.038) nb and sigma(e(+)e(-) -> D+D-)=(2.830 +/- 0.011 +/- 0.026) nb, where the uncertainties are statistical and systematic, respectively.
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| 7. |
- Ablikim, M., et al.
(författare)
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Measurement of the integrated Luminosities of cross-section scan data samples around the psi(3770) mass region
- 2018
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Ingår i: Chinese Physics C. - : SCIENCE PRESS. - 1674-1137 .- 2058-6132. ; 42:6
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the nature of the psi(3770) resonance and to measure the cross section for e(+)e(-) -> D (D) over bar, a cross-section scan data sample, distributed among 41 center-of-mass energy points from 3.73 to 3.89 GeV, was taken with the BESIII detector operated at the BEPCII collider in the year 2010. By analyzing the large angle Bhabha scattering events, we measure the integrated luminosity of the data sample at each center-of-mass energy point. The total integrated luminosity of the data sample is 76.16 +/- 0.04 +/- 0.61 pb(-1), where the first uncertainty is statistical and the second systematic.
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| 8. |
- Ablikim, M., et al.
(författare)
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Observation of psi(3686) -> eta ' e(+)e(-)
- 2018
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Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 783, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- Using a data sample of 448.1 x 10(6) psi(3686) events collected with the BESIII detector at the BEPCII collider, we report the first observation of the electromagnetic Dalitz decay psi(3686) -> eta'e(+)e(-), with significances of 7.0 sigma and 6.3 sigma when reconstructing the eta' meson via its decay modes eta' -> gamma pi(+)pi(-) and eta' -> pi(+)pi(-) eta (eta -> gamma gamma), respectively. The weighted average branching fraction is determined to be B(psi(3686) -> eta'e(+)e(-)) = (1.90 +/- 0.25 +/- 0.11) x 10(-6), where the first uncertainty is statistical and the second systematic.
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| 9. |
- Ablikim, M., et al.
(författare)
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Observation of the Semileptonic Decay D-0 -> a(0)(980)(-)e(+)nu(e) and Evidence for D+ -> a(0)(980)(0)e(+)nu(e)
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:8
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Tidskriftsartikel (refereegranskat)abstract
- Using an e(+)e(-) collision data sample of 2.93 fb(-1) collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of D-0 -> a(0)(980)(-)e(+)nu(e) and evidence for D+ -> a(0)(980)(0)e(+)nu(e) with significances of 6.4 sigma and 2.9 sigma, respectively. The absolute branching fractions are determined to be B(D-0 -> a(0)(980)(-)e(+)nu(e)) x B(a(0)(980)(-) -> eta pi(-)) = [1.33(-0.29)(+0.33)(stat) +/- 0.09(syst)] x 10(-4) and B(D+ -> a(0)(980)(0)e(+)nu(e)) x B(a(0)(980)(0) -> eta pi(0)) = [1.66(-0.66)(+0.81)(stat) +/- 0.11(syst) x 10(-4). This is the first time the a(0)(980) meson has been measured in a D-0 semileptonic decay, which would open one more interesting page in the investigation of the nature of the puzzling a(0)(980) states.
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| 10. |
- Ablikim, M., et al.
(författare)
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Precision Measurement of the e(+)e(-) -> Lambda(+)(c)(Lambda)over-bar(c)(-) Cross Section Near Threshold
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:13
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Tidskriftsartikel (refereegranskat)abstract
- The cross section of the e(+)e(-) -> Lambda(+)(c)(Lambda) over bar (-)(c) process is measured with unprecedented precision using data collected with the BESIII detector at root s = 4574.5, 4580.0, 4590.0 and 4599.5 MeV. The nonzero cross section near the Lambda(+)(c)(Lambda) over bar (-)(c) production threshold is cleared. At center-of-mass energies root s = 4574.5 and 4599.5 MeV, the higher statistics data enable us to measure the Lambda(c) polar angle distributions. From these, the.c electric over magnetic form-factor ratios (vertical bar G(E)/G(M)vertical bar) are measured for the first time. They are found to be 1.14 +/- 0.14 +/- 0.07 and 1.23 +/- 0.05 +/- 0.03, respectively, where the first uncertainties are statistical and the second are systematic.
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