| 401. |
- 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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| 402. |
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| 403. |
- Yang, Yaohua, et al.
(författare)
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Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:3, s. 505-517
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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| 404. |
- Zeng, Z., et al.
(författare)
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Deforestation-induced warming over tropical mountain regions regulated by elevation
- 2021
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 14, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Agriculture is expanding in tropical mountainous areas, yet its climatic effect is poorly understood. Here, we investigate how elevation regulates the biophysical climate impacts of deforestation over tropical mountainous areas by integrating satellite-observed forest cover changes into a high-resolution land–atmosphere coupled model. We show that recent forest conversion between 2000 and 2014 increased the regional warming by 0.022±0.002°C in the Southeast Asian Massif, 0.010±0.007°C in the Barisan Mountains (Maritime Southeast Asia), 0.042±0.010°C in the Serra da Espinhaço (South America) and 0.047±0.008°C in the Albertine Rift mountains (Africa) during the local dry season. The deforestation-driven local temperature anomaly can reach up to 2°C where forest conversion is extensive. The warming from mountain deforestation depends on elevation, through the intertwined and opposing effects of increased albedo causing cooling and decreased evapotranspiration causing warming. As the elevation increases, the albedo effect increases in importance and the warming effect decreases, analogous to previously highlighted decreases of deforestation-induced warming with increasing latitude. As most new croplands are encroaching lands at low to moderate elevations, deforestation produces higher warming from suppressed evapotranspiration. Impacts of this additional warming on crop yields, land degradation and biodiversity of nearby intact ecosystems should be incorporated into future assessments.
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| 405. |
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| 406. |
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| 407. |
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| 408. |
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| 409. |
- Alström, Per, et al.
(författare)
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Integrative taxonomy of the Plain-backed Thrush (Zoothera mollissima) complex (Aves, Turdidae) reveals cryptic species, including a new species.
- 2016
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Ingår i: Avian research. - : Elsevier BV. - 2053-7166. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Plain-backed Thrush Zoothera mollissima breeds in the Himalayas and mountains of central China. It was long considered conspecific with the Long-tailed Thrush Zoothera dixoni, until these were shown to be broadly sympatric. Methods: We revise the Z. mollissima–Z. dixoni complex by integrating morphological, acoustic, genetic (two mito- chondrial and two nuclear markers), ecological and distributional datasets. Results: In earlier field observations, we noted two very different song types of“Plain-backed”Thrush segregated by breeding habitat and elevation. Further integrative analyses congruently identify three groups: an alpine breeder in the Himalayas and Sichuan, China (“Alpine Thrush”); a forest breeder in the eastern Himalayas and northwest Yunnan (at least), China (“Himalayan Forest Thrush”); and a forest breeder in central Sichuan (“Sichuan Forest Thrush”). Alpine and Himalayan Forest Thrushes are broadly sympatric, but segregated by habitat and altitude, and the same is prob- ably true also for Alpine and Sichuan Forest Thrushes. These three groups differ markedly in morphology and songs. In addition, DNA sequence data from three non-breeding specimens from Yunnan indicate that yet another lineage exists (“Yunnan Thrush”). However, we find no consistent morphological differences from Alpine Thrush, and its breed- ing range is unknown. Molecular phylogenetic analyses suggest that all four groups diverged at least a few million years ago, and identify Alpine Thrush and the putative “Yunnan Thrush” as sisters, and the two forest taxa as sisters. Cytochrome b divergences among the four Z. mollissima sensu lato (s.l.) clades are similar to those between any of them and Z. dixoni, and exceed that between the two congeneric outgroup species. We lectotypify the name Oreocin- cla rostrata Hodgson, 1845 with the Z. mollissima sensu stricto (s.s.) specimen long considered its type. No available name unambiguously pertains to the Himalayan Forest Thrush. Conclusions: The Plain-backed Thrush Z. mollissima s.l. comprises at least three species: Alpine Thrush Z. mollissima s.s., with a widespread alpine breeding distribution; Sichuan Forest Thrush Z. griseiceps, breeding in central Sichuan forests; and Himalayan Forest Thrush, breeding in the eastern Himalayas and northwest Yunnan (at least), which is described herein as a new species. “Yunnan Thrush” requires further study.
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| 410. |
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