| 1. |
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Thomas, HS, et al.
(författare)
-
- 2019
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swepub:Mat__t
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| 8. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 13. |
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| 14. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 15. |
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| 16. |
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| 17. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 18. |
- Adler, SS, et al.
(författare)
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Bose-Einstein correlations of charged pion pairs in Au+Au collisions at root(NN)-N-s = 200 GeV
- 2004
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Ingår i: Physical Review Letters. - 1079-7114. ; 93:15
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Tidskriftsartikel (refereegranskat)abstract
- Bose-Einstein correlations of identically charged pion pairs were measured by the PHENIX experiment at midrapidity in Au+Au collisions at roots(NN)=200 GeV. The Bertsch-Pratt radius parameters were determined as a function of the transverse momentum of the pair and as a function of the centrality of the collision. Using the standard core-halo partial Coulomb fits, and a new parametrization which constrains the Coulomb fraction as determined from the unlike-sign pion correlation, the ratio R-out/R-side is within 0.8-1.1 for 0.25<<1.2 GeV/c. The centrality dependence of all radii is well described by a linear scaling in N-part(1/3), and R-out/R-side for similar to0.45 GeV/c is approximately constant at unity as a function of centrality.
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| 19. |
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| 20. |
- Adler, SS, et al.
(författare)
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Common suppression pattern of eta and pi(0) mesons at high transverse momentum in Au plus Au collisions at root SNN=200 GeV
- 2006
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Ingår i: Physical Review Letters. - 1079-7114. ; 96:20
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Tidskriftsartikel (refereegranskat)abstract
- Inclusive transverse momentum spectra of eta mesons have been measured within p(T)=2-10 GeV/c at midrapidity by the PHENIX experiment in Au+Au collisions at root s(NN) = 200 GeV. In central Au+Au the eta yields are significantly suppressed compared to peripheral Au+Au, d+Au, and p+p yields scaled by the corresponding number of nucleon-nucleon collisions. The magnitude, centrality, and p(T) dependence of the suppression is common, within errors, for eta and pi(0). The ratio of eta to pi(0) spectra at high p(T) amounts to 0.40 < R-eta/pi(0)< 0.48 for the three systems, in agreement with the world average measured in hadronic and nuclear reactions and, at large scaled momentum, in e(+)e(-) collisions.
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| 21. |
- Adler, SS, et al.
(författare)
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Deuteron and antideuteron production in Au+Au collisions at root s(NN)=200 GeV
- 2005
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Ingår i: Physical Review Letters. - 1079-7114. ; 94:12
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Tidskriftsartikel (refereegranskat)abstract
- The production of deuterons and antideuterons in the transverse momentum range 1.1 < p(T)< 4.3 GeV/c at midrapidity in Au+Au collisions at root s(NN) = 200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis, comparing the deuteron and antideuteron spectra with that of proton and antiproton, has been performed. The coalescence probability is equal for both deuterons and antideuterons and it increases as a function of p(T), which is consistent with an expanding collision zone. Comparing (anti)proton yields, (p) over bar /p = 0.73 +/- 0.01, with (anti)deuteron yields, (d) over bar /d = 0.47 +/- 0.03, we estimate that (n) over bar /n = 0.64 +/- 0.04. The nucleon phase space density is estimated from the coalescence measurement.
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| 22. |
- Adler, SS, et al.
(författare)
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Elliptic flow of identified hadrons in Au+Au collisions at root s(NN)=200 GeV
- 2003
-
Ingår i: Physical Review Letters. - 1079-7114. ; 91:18: 182301
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Tidskriftsartikel (refereegranskat)abstract
- The anisotropy parameter (v(2)), the second harmonic of the azimuthal particle distribution, has been measured with the PHENIX detector in Au+Au collisions at roots(NN)=200 GeV for identified and inclusive charged particle production at central rapidities (eta<0.35) with respect to the reaction plane defined at high rapidities (eta=3-4 ). We observe that the v(2) of mesons falls below that of (anti)baryons for p(T)>2 GeV/c, in marked contrast to the predictions of a hydrodynamical model. A quark-coalescence model is also investigated.
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| 23. |
- Adler, SS, et al.
(författare)
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J/psi production from proton-proton collisions at root s=200 GeV
- 2004
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Ingår i: Physical Review Letters. - 1079-7114. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- J/psi production has been measured in proton-proton collisions at roots=200 GeV over a wide rapidity and transverse momentum range by the PHENIX experiment at the Relativistic Heavy Ion Collider. Distributions of the rapidity and transverse momentum, along with measurements of the mean transverse momentum and total production cross section are presented and compared to available theoretical calculations. The total J/psi cross section is 4.0+/-0.6(stat)+/-0.6(syst)+/-0.4(abs) mub. The mean transverse momentum is 1.80+/-0.23(stat)+/-0.16(syst) GeV/c.
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| 24. |
- Adler, SS, et al.
(författare)
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J/psi production in Au-Au collisions at root s(NN)=200 GeV
- 2004
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 69:1
-
Tidskriftsartikel (refereegranskat)abstract
- First results on charm quarkonia production in heavy ion collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The yield of J/psi's measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au-Au reactions at roots(NN) = 200 GeV is analyzed as a function of collision centrality. For this analysis we have studied 49.3x10(6) minimum bias Au-Au reactions. We present the J/psi invariant yield dN/dy for peripheral and midcentral reactions. For the most central collisions where we observe no signal above background, we quote 90% confidence level upper limits. We compare these results with our J/psi measurement from proton-proton reactions at the same energy. We find that our measurements are not consistent with models that predict strong enhancement relative to binary collision scaling.
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| 25. |
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| 26. |
- Adler, SS, et al.
(författare)
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Measurement of single electron event anisotropy in Au plus Au collisions at root s(NN)=200 GeV
- 2005
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 72:2
-
Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum dependence of the azimuthal anisotropy parameter v(2), the second harmonic of the azimuthal distribution, for electrons at midrapidity (vertical bar eta vertical bar < 0.35) has been measured with the PHENIX detector in Au+Au collisions at root s(NN) = 200 GeV. The measurement was made with respect to the reaction plane defined at high rapidities (vertical bar eta vertical bar = 3.1-3.9). From the result we have measured the v(2) of electrons from heavy flavor decay after subtraction of the v(2) of electrons from other sources such as photon conversions and Dalitz decay from light neutral mesons. We observe a nonzero single electron v(2) with a 90% confidence level in the intermediate-p(T) region. The precision of the present data set does not permit us to conclude definitively that heavy quarks exhibit thermalization with the transverse flow of the bulk matter.
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| 27. |
- Adler, SS, et al.
(författare)
-
Midrapidity direct-photon production in p+p collisions at root s=200 GeV
- 2005
-
Ingår i: Physical Review D (Particles and Fields). - 0556-2821. ; 71:7
-
Tidskriftsartikel (refereegranskat)abstract
- A measurement of direct photons in p+p collisions at root s=200 GeV is presented. A photon excess above background from pi(0)->gamma+gamma, eta ->gamma+gamma and other decays is observed in the transverse momentum range 5.5 < p(T)< 7 GeV/c. The result is compared to a next-to-leading-order perturbative QCD calculation. Within errors, good agreement is found between the QCD calculation and the measured result.
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| 28. |
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| 29. |
- Adler, SS, et al.
(författare)
-
Production of phi mesons at midrapidity in root S-NN=200 GeVAu+Au collisions at relativistic energies
- 2005
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 72:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of phi meson production in the K+K- decay channel from Au+Au collisions at root s(NN) =200 GeV as measured at midrapidity by the PHENIX detector at Brookhaven National Laboratory's Relativistic Heavy Ion Collider. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the Particle Data Group accepted values is observed, contrary to some model predictions. The phi transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. However, when these data are fitted by a hydrodynamic model the result is that the centrality-dependent freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting identified charged hadron data. As a function of transverse momentum the collisions scaled peripheral-to-central yield ratio R-CP for the phi is comparable to that of pions rather than that of protons. This result lends support to theoretical models that distinguish between baryons and mesons instead of particle mass for explaining the anomalous (anti) proton yield.
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| 30. |
- Adler, SS, et al.
(författare)
-
Scaling properties of proton and antiproton production in root s(NN)=200 GeV Au+Au collisions
- 2003
-
Ingår i: Physical Review Letters. - 1079-7114. ; 91:17: 172301
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the yield of protons and antiprotons, as a function of centrality and transverse momentum, in Au+Au collisions at rootS(NN)=200 GeV measured at midrapidity by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider. In central collisions at intermediate transverse momenta (1.5
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Romanelli, F, et al.
(författare)
-
Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
-
Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 41. |
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| 42. |
- Adcox, K, et al.
(författare)
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PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 43. |
- Adler, SS, et al.
(författare)
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Improved measurement of double helicity asymmetry in inclulsive midrapidity pi(0) production for polarized p+p collisions at root s=200 GeV
- 2006
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 73:9
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Tidskriftsartikel (refereegranskat)abstract
- We present an improved measurement of the double helicity asymmetry for pi(0) production in polarized proton-proton scattering at root s=200 GeV employing the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The improvements to our previous measurement come from two main factors: Inclusion of a new data set from the 2004 RHIC run with higher beam polarizations than the earlier run and a recalibration of the beam polarization measurements for the earlier run, which resulted in reduced uncertainties and increased beam polarizations. The results are compared to a Next to Leading Order (NLO) perturbative Quantum Chromodynamics (pQCD) calculation with a range of polarized gluon distributions.
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| 44. |
- Adler, SS, et al.
(författare)
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Measurement of transverse single-spin asymmetries for midrapidity production of neutral pions and charged hadrons in polarized p+p collisions at root s=200 GeV
- 2005
-
Ingår i: Physical Review Letters. - 1079-7114. ; 95
-
Tidskriftsartikel (refereegranskat)abstract
- Transverse single-spin asymmetries to probe the transverse-spin structure of the proton have been measured for neutral pions and nonidentified charged hadrons from polarized proton-proton collisions at midrapidity and root s = 200 GeV. The data cover a transverse momentum (pT) range 1.0-5.0 GeV/c for neutral pions and 0.5-5.0 GeV/c for charged hadrons, at a Feynman-x value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within errors of a few percent. In addition, the inclusive charged hadron cross section at midrapidity from 0.5 < P-T < 7.0 GeV/c is presented and compared to next-to-leading order perturbative QCD ( pQCD) calculations. Successful description of the unpolarized cross section above similar to 2 GeV/c suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.
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| 45. |
- Adler, SS, et al.
(författare)
-
Single electrons from heavy-flavor decays in p + p collisions at root s=200 GeV
- 2006
-
Ingår i: Physical Review Letters. - 1079-7114. ; 96:3
-
Tidskriftsartikel (refereegranskat)abstract
- The invariant differential cross section for inclusive electron production in p+p collisions at root s=200 GeV has been measured by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider over the transverse momentum range 0.4 <= p(T) <= 5.0 GeV/c in the central rapidity region (vertical bar eta vertical bar <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e., charm quarks or, at high p(T), bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy-flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined to be sigma(c (c) over bar) = 0.92 +/- 0.15(stat) +/- 0.54(syst) mb.
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| 46. |
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| 47. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 48. |
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| 49. |
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| 50. |
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