GWAS筛查多民族癌症易感基因
发表于： 6.1影响因子 PLoS Genet. 2013 Mar ， 使用的是 能覆盖 191,032 common and rare nonsynonymous, splice site, or nonsense variants 位点是 Illumina HumanExome SNP array，此cohort 纳入了
- 2,984 breast cancer cases
- 4,376 prostate cancer cases
- 7,545 controls
人群队列是多民族的，Of the 15,837 samples, 14,905 were included in the analysis
- 3,315 European Americans
- 3,854 African Americans
- 3,106 Latinos, 3,843 Japanese Americans
- 787 Native Hawaiians
整体人群队列的GAWS分析结果确定的显著性基因有：
- 乳腺癌的 ： LDLRAD1, SLC19A1, FGFBP3, CASP5, MMAB, SLC16A6, and INS-IGF2
- 前列腺癌 ： F13A1, ANXA4, MANSC1, and GP6
其实乳腺癌患者可以分成
- estrogen receptor-positive (ER+) cases (n = 1,688)
- ER- breast cancer (n = 441 cases)
这样就可以分开计算GWAS的显著性。
芯片过滤
需要剔除不合格的样本及位点
原始芯片是 Illumina Human Exome BeadChip (n = 247,895 SNPs) ，过滤后是 27,506 SNPs.
原始人群是15,837 samples, 过滤后是 14,905
芯片数据结果
All SNPs were analyzed and their results shown in Tables S1, S2, S3, S4, S5, S6, S7, S8, S9.
但是GWAS分析，只纳入了 191,032 putative functional variants in the following categories (NS, SP and stop gain or loss) that passed quality control procedures discussed above.
主成分分析判断人群
使用的是 EIGENSTRAT 文章提到的 2,887 autosomal ancestry informative markers on the array
有一个新的，更大样本的研究： 5.34 影响因子 Hum Mol Genet. 2016 Aug
We conducted a two-stage genome-wide association study (GWAS) including 14 224 cases and 14 829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer.
第一阶段人群是：a total of 7619 cases and 6286 controls，使用的是各种各样的Affymetrix芯片
- 4866 Chinese women (SBCGS)
- 4298 Korean women (SeBCS1)
- 4741 Japanese women (BBJ1)
第二阶段使用的是 iPLEX Sequenom MassArray platform for 15 148 samples
- KOHBRA/KoGES
- HCES-Br
- SeBCS2
- Nagoya
- Nagano
这个GWAS主要是报道两个风险位点
- rs12118297 at 1p22.3 (near the LMO4 gene)
- rs16992204 at 21q22.12 (near the LINC00160 gene)
所翻译原文链接：https://www.ncbi.nlm.nih.gov/pubmed/23555315