Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.
Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.
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DOI：
10.1002/jgh3.12682
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Wang Z;Budhu AS;Shen Y;Wong LL;Hernandez BY;Tiirikainen M;Ma X;Irwin ML;Lu L;Zhao H;Lim JK;Taddei T;Mishra L;Pawlish K;Stroup A;Brown R;Nguyen MH;Koshiol J;Hernandez MO;Forgues M;Yang HI;Lee MH;Huang YH;Iwasaki M;Goto A;Suzuki S;Matsuda K;Tanikawa C;Kamatani Y;Mann D;Guarnera M;Shetty K;Thomas CE;Yuan JM;Khor CC;Koh WP;Risch H;Wang XW;Yu H
慢性丙型肝炎病毒（HCV）感染，长期饮酒，吸烟和肥胖是美国肝细胞癌（HCC）的主要危险因素，但具有这些因素的个体之间的疾病风险差异很大，表明宿主对HCC的易感性和基因-环境相互作用。为了解决HCC的遗传易感性，我们进行了全基因组关联研究（GWAS）。在美国进行了两项关于肝细胞癌的病例对照研究。使用Illumian微阵列芯片对超过710 000个单核苷酸多态性（SNP）的DNA样本进行基因分型。我们比较了705例HCC病例和1455例人群对照的这些SNP与HCC的相关性，并在其他研究中验证了我们的发现。在这个GWAS中，我们发现在调整年龄，性别和前三个主成分（PC）后，两个SNP在P <5E-8时与HCC相关，六个SNP在P < 5E-6时与HCC相关。在一项小型美国病例对照研究和一项新加坡队列研究中，复制了染色体22 q13.31中的5个SNP，PNPLA 3中的3个（rs 2281135、rs 2896019和rs 4823173）和SAMM 50中的2个（rs3761472、rs3827385）。在调整体重指数和HCV感染后，这种关联仍然显着。多个数据集的Meta分析表明，这些SNP与HCC显著相关。PNPLA 3和SAMM 50中的SNP是已知的非酒精性脂肪肝（NAFLD）风险位点，并被怀疑与HCC相关。我们的GWAS证明了这些SNP与美国人群中HCC的相关性。这种关系的生物学机制仍有待阐明。全基因组关联研究（GWAS）显示，22q13.31中的5个SNP，PNPLA 3中的3个（rs 2281135，rs 2896019和4823173）和SAMM 50中的2个（rs3761472和rs3827385）与美国的HCC相关。
Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. In this GWAS, we found that two SNPs were associated with HCC at P < 5E‐8 and six SNPs at P < 5E‐6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case‐control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta‐analysis of multiple datasets indicated that these SNPs were significantly associated with HCC. SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated. Genome‐wide association study (GWAS) showed that five SNPs in 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and 4823173) and two in SAMM50 (rs3761472 and rs3827385), were associated with HCC in the United States.
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影响因子：
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作者：
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影响因子：
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作者：
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Moldes, Marthe
影响因子：
7.7
作者：
Kershaw, EE;Hamm, JK;Flier, JS
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Flier, JS
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N