Population stratification is a problem in genetic association studies because it is likely to highlight loci that underlie the population structure rather than disease-related loci. At present, principal component ana...Population stratification is a problem in genetic association studies because it is likely to highlight loci that underlie the population structure rather than disease-related loci. At present, principal component analysis （PCA） has been proven to be an effective way to correct for population stratification. However, the conventional PCA algorithm is time-consuming when dealing with large datasets. We developed a Graphic processing unit （GPU）-based PCA software named SHEsisPCA （http：//analysis.bio-x.cn/SHEsisMain.htm） that is highly parallel with a highest speedup greater than 100 compared with its CPU version. A cluster algorithm based on X-means was also implemented as a way to detect population subgroups and to obtain matched cases and controls in order to reduce the genomic inflation and increase the power. A study of both simulated and real datasets showed that SHEsisPCA ran at an extremely high speed while the accuracy was hardly reduced. Therefore, SHEsisPCA can help correct for population stratification much more efficiently than the conventional CPU-based algorithms.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of ...BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular ge展开更多
目的:探索中国人群中叶酸/同型半胱氨酸代谢通路上的基因多态性与非综合征型唇腭裂(isolated non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:在806个中国人群的核心家庭...目的:探索中国人群中叶酸/同型半胱氨酸代谢通路上的基因多态性与非综合征型唇腭裂(isolated non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:在806个中国人群的核心家庭中,对叶酸/同型半胱氨酸通路上的18个基因进行了传递不平衡检验以及基因-环境交互作用分析。环境因素包括母亲孕期吸烟、被动吸烟、饮酒及服用多维生素补充剂。结果:经过质量控制的筛选,共对257个位点的单核苷酸多态性(single nucleotide polymorphisms,SNPs)进行了传递不平衡检验及交互作用分析,结果显示,共有4个SNPs(rs6428977、rs12060264、rs7730643和rs4920037)与NSCL/P显著关联(P<0.05)。但在Bon-ferroni校正后,该通路上的代谢基因位点与NSCL/P之间的关联不具有统计学意义。经多重检验校正后,未发现常见孕期环境暴露与叶酸/同型半胱氨酸代谢通路上的基因多态性存在显著的交互作用。结论:未发现叶酸/同型半胱氨酸代谢通路上的基因多态性与NSCL/P之间存在关联。展开更多
目的:探索中国人群中细胞黏附相关基因多态性与非综合征型唇裂合并或不合并腭裂(isolated nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:对一项国际多中心的全基因组关...目的:探索中国人群中细胞黏附相关基因多态性与非综合征型唇裂合并或不合并腭裂(isolated nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:对一项国际多中心的全基因组关联研究(genome-wide association study,GWAS)的数据进行再分析,选取其中806个中国人群NSCL/P核心家庭,对该人群的8个细胞黏附相关基因包括CDH1、CTNNB1、PVRL1、PVRL2、PVRL3、ACTN1、VCL、LEF1进行了传递不平衡检验(transmisssion diseqilibrium test,TDT)及基因-环境交互作用分析。环境因素包括患儿母亲孕期吸烟、被动吸烟、饮酒及服用多种维生素。结果:经数据质量控制后,共纳入226个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,TDT结果显示,CTNNB1、CDH1、ACTN1基因中有23个SNPs与NSCL/P之间存在关联(P<0.05),但经Bonferroni校正后,这些关联均无统计学意义(P>0.000 2)。基因-环境交互作用的分析结果显示,14号染色体的ACTN1基因中rs743127位点与母亲孕期被动吸烟的交互作用具有统计学意义(P=0.000 1),母亲孕期无被动吸烟时携带一个该危险位点的患儿的OR值为0.59(95%CI:0.38-0.90),患儿母亲孕期中有被动吸烟情况时携带一个危险位点的患儿的OR值为2.00(95%CI:1.23-3.26)。而ACTN1基因的rs1475034、rs370535、rs2273419位点、CTNNB1基因的rs106871位点与被动吸烟和PVRL3基因的rs7634000、rs2971366、rs2634553、rs1489032、rs7624812位点与母亲孕期补充维生素的交互作用并无统计学意义(P>0.000 2)。结论:传递不平衡检验未发现所纳入的细胞黏附相关基因多态性与NSCL/P存在关联,但基因-环境交互作用分析结果提示,ACTN1基因可能通过基因-环境交互作用而影响NSCL/P的发病风险。展开更多
基金supported by the National Key Basic Research Program of China (973 Program) (No. 2015CB559100)the National High Technology Research and Development Program of China (863 Program) (Nos. 2012AA02A515 and2012AA021802)+2 种基金the Natural Science Foundation of China (Nos. 31325014, 81130022, 81272302 and 81421061)the National Program for Support of Top-Notch Young Professionals, the Program of Shanghai Subject Chief Scientist (No. 15XD1502200)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 12SG17)
文摘Population stratification is a problem in genetic association studies because it is likely to highlight loci that underlie the population structure rather than disease-related loci. At present, principal component analysis （PCA） has been proven to be an effective way to correct for population stratification. However, the conventional PCA algorithm is time-consuming when dealing with large datasets. We developed a Graphic processing unit （GPU）-based PCA software named SHEsisPCA （http：//analysis.bio-x.cn/SHEsisMain.htm） that is highly parallel with a highest speedup greater than 100 compared with its CPU version. A cluster algorithm based on X-means was also implemented as a way to detect population subgroups and to obtain matched cases and controls in order to reduce the genomic inflation and increase the power. A study of both simulated and real datasets showed that SHEsisPCA ran at an extremely high speed while the accuracy was hardly reduced. Therefore, SHEsisPCA can help correct for population stratification much more efficiently than the conventional CPU-based algorithms.
基金Supported by National Natural Science Foundation of China,No.81601692Program of Liaoning Province Department of Education,No.LK2016002
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular ge
文摘目的:探索中国人群中叶酸/同型半胱氨酸代谢通路上的基因多态性与非综合征型唇腭裂(isolated non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:在806个中国人群的核心家庭中,对叶酸/同型半胱氨酸通路上的18个基因进行了传递不平衡检验以及基因-环境交互作用分析。环境因素包括母亲孕期吸烟、被动吸烟、饮酒及服用多维生素补充剂。结果:经过质量控制的筛选,共对257个位点的单核苷酸多态性(single nucleotide polymorphisms,SNPs)进行了传递不平衡检验及交互作用分析,结果显示,共有4个SNPs(rs6428977、rs12060264、rs7730643和rs4920037)与NSCL/P显著关联(P<0.05)。但在Bon-ferroni校正后,该通路上的代谢基因位点与NSCL/P之间的关联不具有统计学意义。经多重检验校正后,未发现常见孕期环境暴露与叶酸/同型半胱氨酸代谢通路上的基因多态性存在显著的交互作用。结论:未发现叶酸/同型半胱氨酸代谢通路上的基因多态性与NSCL/P之间存在关联。
文摘目的:探索中国人群中细胞黏附相关基因多态性与非综合征型唇裂合并或不合并腭裂(isolated nonsyndromic cleft lip with or without cleft palate,NSCL/P)的关联关系及可能存在的基因-环境交互作用。方法:对一项国际多中心的全基因组关联研究(genome-wide association study,GWAS)的数据进行再分析,选取其中806个中国人群NSCL/P核心家庭,对该人群的8个细胞黏附相关基因包括CDH1、CTNNB1、PVRL1、PVRL2、PVRL3、ACTN1、VCL、LEF1进行了传递不平衡检验(transmisssion diseqilibrium test,TDT)及基因-环境交互作用分析。环境因素包括患儿母亲孕期吸烟、被动吸烟、饮酒及服用多种维生素。结果:经数据质量控制后,共纳入226个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,TDT结果显示,CTNNB1、CDH1、ACTN1基因中有23个SNPs与NSCL/P之间存在关联(P<0.05),但经Bonferroni校正后,这些关联均无统计学意义(P>0.000 2)。基因-环境交互作用的分析结果显示,14号染色体的ACTN1基因中rs743127位点与母亲孕期被动吸烟的交互作用具有统计学意义(P=0.000 1),母亲孕期无被动吸烟时携带一个该危险位点的患儿的OR值为0.59(95%CI:0.38-0.90),患儿母亲孕期中有被动吸烟情况时携带一个危险位点的患儿的OR值为2.00(95%CI:1.23-3.26)。而ACTN1基因的rs1475034、rs370535、rs2273419位点、CTNNB1基因的rs106871位点与被动吸烟和PVRL3基因的rs7634000、rs2971366、rs2634553、rs1489032、rs7624812位点与母亲孕期补充维生素的交互作用并无统计学意义(P>0.000 2)。结论:传递不平衡检验未发现所纳入的细胞黏附相关基因多态性与NSCL/P存在关联,但基因-环境交互作用分析结果提示,ACTN1基因可能通过基因-环境交互作用而影响NSCL/P的发病风险。
