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| 2. |
- Haycock, Philip C., et al.
(author)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Journal article (peer-reviewed)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Langefeld, Carl D., et al.
(author)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 4. |
- Machiela, Mitchell J., et al.
(author)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Journal article (peer-reviewed)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 5. |
- Quimby, Robert M., et al.
(author)
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Spectra of Hydrogen-poor Superluminous Supernovae from the Palomar Transient Factory
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 855:1, s. 1-57
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Journal article (peer-reviewed)abstract
- Most Type I superluminous supernovae (SLSNe-I) reported to date have been identified by their high peak luminosities and spectra lacking obvious signs of hydrogen. We demonstrate that these events can be distinguished from normal-luminosity SNe (including Type Ic events) solely from their spectra over a wide range of light-curve phases. We use this distinction to select 19 SLSNe-I and four possible SLSNe-I from the Palomar Transient Factory archive (including seven previously published objects). We present 127 new spectra of these objects and combine these with 39 previously published spectra, and we use these to discuss the average spectral properties of SLSNe-I at different spectral phases. We find that Mn II most probably contributes to the ultraviolet spectral features after maximum light, and we give a detailed study of the O II features that often characterize the early-time optical spectra of SLSNe-I. We discuss the velocity distribution of O II, finding that for some SLSNe-I this can be confined to a narrow range compared to relatively large systematic velocity shifts. Mg II and Fe II favor higher velocities than O II and C II, and we briefly discuss how this may constrain power-source models. We tentatively group objects by how well they match either SN 2011ke or PTF12dam and discuss the possibility that physically distinct events may have been previously grouped together under the SLSN-I label.
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| 6. |
- Hoffmann, Samantha L., et al.
(author)
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OPTICAL IDENTIFICATION OF CEPHEIDS IN 19 HOST GALAXIES OF TYPE Ia SUPERNOVAE AND NGC 4258 WITH THE HUBBLE SPACE TELESCOPE
- 2016
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 830:1
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Journal article (peer-reviewed)abstract
- We present results of an optical search conducted as part of the SH0ES project (Supernovae and H-0 for the Equation of State of dark energy) for Cepheid variable stars using the Hubble Space Telescope (HST) in 19 hosts of Type Ia supernovae (SNe Ia) and the maser-host galaxy NGC 4258. The targets include nine newly imaged SN. Ia hosts using a novel strategy based on a long-pass filter that minimizes the number of HST orbits required to detect and accurately determine Cepheid properties. We carried out a homogeneous reduction and analysis of all observations, including new universal variability searches in all SN. Ia hosts, which yielded a total of 2200 variables with well-defined selection criteria, the largest such sample identified outside the Local Group. These objects are used in a companion paper to determine the local value of H-0 with a total uncertainty of 2.4%.
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| 7. |
- Ben-Ami, Sagi, et al.
(author)
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ULTRAVIOLET SPECTROSCOPY OF TYPE IIB SUPERNOVAE : DIVERSITY AND THE IMPACT OF CIRCUMSTELLAR MATERIAL
- 2015
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 803:1
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Journal article (peer-reviewed)abstract
- We present new Hubble Space Telescope (HST) multi-epoch ultraviolet (UV) spectra of the bright Type IIb SN 2013df, and undertake a comprehensive analysis of the set of four SNe IIb for which HST UV spectra are available (SN 1993J, SN 2001ig, SN 2011dh, and SN 2013df). We find strong diversity in both continuum levels and line features among these objects. We use radiative-transfer models that fit the optical part of the spectrum well, and find that in three of these four events we see a UV continuum flux excess, apparently unaffected by line absorption. We hypothesize that this emission originates above the photosphere, and is related to interaction with circumstellar material (CSM) located in close proximity to the SN progenitor. In contrast, the spectra of SN 2001ig are well fit by single-temperature models, display weak continuum and strong reverse-fluorescence features, and are similar to spectra of radioactive 56Ni-dominated SNe Ia. A comparison of the early shock-cooling components in the observed light curves with the UV continuum levels which we assume trace the strength of CSM interaction suggests that events with slower cooling have stronger CSM emission. The radio emission from events having a prominent UV excess is perhaps consistent with slower blast-wave velocities, as expected if the explosion shock was slowed down by the CSM that is also responsible for the strong UV, but this connection is currently speculative as it is based on only a few events.
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