Browsing by Author "Zhu, B."
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Item Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33(Human Molecular Genetics, 2014-07) Wang, Z.; Zhu, B.; Zhang, M.; Parikh, H.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. (PDF) Imputation and subset based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Available from: https://www.researchgate.net/publication/264461524_Imputation_and_subset_based_association_analysis_across_different_cancer_types_identifies_multiple_independent_risk_loci_in_the_TERT-CLPTM1L_region_on_chromosome_5p1533 [accessed Nov 08 2018].Item Origin of sapphirine- and garnet-bearing clinopyroxenite xenoliths entrained in the Jiande basalts, SE China(Lithos, 2018-04) Xiao, Y.; Zhang, H.F.; Liang, Z.; Su, B.X.; Zhu, B.; Sakyi, P.A.We present petrological and geochemical data of sapphirine- and garnet-bearing clinopyroxenite xenoliths entrained in the Jiande Cenozoic basalts, SE China, to investigate their igneous and metamorphic history, and reconstruct of the thermal-tectonic evolution of the lithospheric mantle. These xenoliths have an unusual mineral association consisting of clinopyroxene + garnet/kelyphite + spinel (±sapphirine). Clinopyroxene has high Mg# (89–93) and displays convex-upward REE pattern. Garnet, partially to completely kelyphitized, is rich in pyrope end-member. It usually includes relics of spinel, suggesting that garnet was formed at the expense of spinel. The spinel has high MgO (20.8–22.9 wt%) and Al2O3 (64.8–67.9 wt%) contents. Sapphirine, forming a rim on spinel, has homogeneous SiO2 (14.5–14.9 wt%), Al2O3 (60.9–61.7 wt%) and MgO (19.7–20.1 wt%) contents, interpreted to be of metamorphic origin. The subsolidus reaction for the formation of sapphirine is as follows: spinel + garnet = sapphirine + clinopyroxene + orthopyroxene. Thus, the earliest mineral assemblage recorded in these xenoliths was spinel + clinopyroxene. The clinopyroxene in the Jiande clinopyroxenite xenoliths has Li abundances (1.04–1.63 ppm) similar to high-P mafic cumulate but much lower than those in crustal eclogite. In addition, the clinopyroxene and garnet do not show positive Eu anomalies. Therefore, the protolith of these three clinopyroxenite xenoliths was most likely a pyroxenite, originating as clinopyroxene + spinel cumulates from mafic melts percolating through the mantle. Many reaction textures such as formation of garnet and sapphirine were developed during decompression possibly coupled with cooling and melt percolation. During this process, the earlier composition of clinopyroxene and spinel also changed. The latest P-T conditions recorded in these xenoliths were at pressure of 8–10 kbar and temperatures of 1069–1094 °C. These observations imply that these rocks have been tectonically uplifted to shallower levels. The uplift process may have been related to lithospheric thinning process accompanied by lithosphere extension and upwelling of the asthenosphere in eastern China.Item Subduction-driven heterogeneity of the lithospheric mantle beneath the Cathaysia block, South China(Journal of Asian Earth Sciences, 2019-10-03) Sakyi, P.A.; Xiao, Y.; Zhang, H.F.; Su, B.X.; Liang, Z.; Zhu, B.To evaluate the modification of the lithospheric mantle by the Paleo-Pacific Ocean subduction beneath the Cathaysia block, we report major and trace elements, and Li isotopes of olivine from Niutoushan, Mingxi, Xilong and Jiande peridotite xenoliths in South China. Spoon-shaped, convex-upward and highly LREE-enriched chondrite-normalized REE patterns of clinopyroxene in the Niutoushan, Mingxi and Xilong xenoliths reflect the interplay between partial melting and subsequent enrichment by metasomatism. Lithium isotope systematics indicate that at least two different metasomatic events affected these peridotites. High Li concentrations in clinopyroxene (up to 59.1 ppm) are ascribed to diffusive Li influx from silicate melts. Olivine grains with lower diffusivity of Li have much higher Li concentrations (0.56–9.76 ppm) and lighter δ7Li values (−52.75 to +10.49‰) than those in the Jiande and other peridotite xenoliths worldwide, showing a prominent carbonatitemetasomatic signature occurring before silicate metasomatism. In addition, increasing Li concentrations of olivine and clinopyroxene with increasing distance from the present subduction trench is consistent with those of low δ26Mg basalts in South China, indicating that the metasomatic agent was related to the westward subduction of the Paleo-Pacific slab. The Jiande lherzolite xenoliths further away from the trench show ‘mantle-like’ Li features and may represent upwelling asthenospheric materials accreted to the continent. Therefore, both types of metasomatism as well as upwelling asthenosphere could have played an important role in the modification of the chemical composition of the mantle beneath the Cathaysia block