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GWAS研究麻风病

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发表于 2017-3-1 10:04:25 | 显示全部楼层 |阅读模式
全文:http://www.nature.com/ng/journal/v47/n3/pdf/ng.3212.pdf
http://www.nature.com/ng/journal/v47/n3/full/ng.3212.html

样本量很可观:
We performed a joint analysis of all the samples from the 3 stages, totaling 8,313 cases and 16,017 controls, using a fixed-effects meta-analysis.
用的 Illumina Human 660K-Quad BeadChips. 这个平台的芯片

芯片数据过滤步骤很严格:
SNP quality control was based on the following criteria: we removed all copy number variations (CNVs) and intensity-only SNPs (95,806 SNPs),
SNPs located in the idiochromosome (16,703 SNPs),
SNPs with call rate <90% (1,271 SNPs),
SNPs with minor allele frequency (MAF) <1% in cases and controls (68,327 SNPs),
SNPs with significant deviation from Hardy-Weinberg equilibrium in controls (P < 1 × 10−8; 998 SNPs) and
SNPs with undetermined clusters (2 SNPs).
Finally, a total of 467,552 genotyped SNPs overlapping with the first independent data set were used as the basis for imputation and genome-wide association analysis.


样本描述,收集过程以及数据分析分成了三期:
We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls.


一期包括两个独立的数据:
a previously published GWAS data set of 706 leprosy cases, 1,225 healthy controls and 4,362 individuals with immune-related diseases as population controls from northern China of Chinese Han descent9  (Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.)
a new unpublished data set of 842 leprosy cases and 925 controls from northern (Chinese Han descent) and southern (Chinese Han descent and minority ancestry groups) China
这两个数据综合起来是:
Meta-analysis of the 2 independent data sets investigated 4,577,171 common SNPs (467,552 genotyped and 4,109,619 imputed) in a total of 1,548 cases and 6,512 controls.
并不是简单的一加一,样本经过了严格的统计学过滤筛选。

二期数据:2,761 leprosy cases and 3,038 controls from northern China of Chinese Han descent
选择的是一期项目得到的top SNPs from 917 independent new loci

三期数据
These 16 SNPs were selected for further validation in 5 additional independent sample series from different regions in China with a total of 4,004 cases and 6,467 controls (stage 3)

也利用过公共数据库:
We carried out a systematic evaluation of the pleiotropic effects of the leprosy susceptibility loci by searching for reported associations of these loci with other diseases in the National Human Genome Research Institute (NHGRI) GWAS catalog


发现样本描述的好复杂
In the discovery stage (stage 1), two independent studies were evaluated. The first study consisted of 706 individuals with leprosy, 1,225 healthy controls and 4,362 individuals with immune-related diseases as population controls, all from northern China and of Chinese Han descent as described in our previous GWAS publication9, 10.
The second study consisted of 955 individuals with leprosy and 1,040 controls recruited from China between 2006–2011, including 436 cases and 533 controls of Chinese Han descent from northern China, 289 cases and 305 controls of Chinese Han descent from southern China, and 230 cases and 202 controls of Chinese Chuang descent and other minority groups from southern China.

Two independent sample series were used in the validation stages.
In the first validation stage (stage 2), 2,761 cases and 3,038 controls of Chinese Han descent were recruited from northern China.

In the second replication phase (stage 3), we recruited samples from multiple regions and ancestry groups in China (Supplementary Fig. 4), including 277 cases and 2,626 controls of from northern China of Chinese Han descent, 1,494 cases and 1,474 controls from southwestern China of Chinese Han descent, 418 cases and 306 controls from southeastern China of Chinese Han descent, 418 cases and 395 controls from western China of Chinese Han descent, and 1,397 cases and 1,666 controls from southern China for minority ancestry groups.
In total, there were 6,765 cases and 9,505 controls used in the validation stages.

样本地域差异:
In the stage 2 validation analysis, all of the cases and controls were Chinese Han from northern China.
In stage 3, the samples were from five regions or subpopulations:
Chinese Han from northern,
southwestern,
southeastern and
western China and
minority groups from southern China.

用到了好多软件:
URLs.

National Human Genome Research Institute (NHGRI) GWAS Catalog,http://www.genome.gov/gwastudies/; PLINK, http://pngu.mgh.harvard.edu/~purcell/plink/; SHAPEIT, https://mathgen.stats.ox.ac.uk/g ... apeit/shapeit.html; IMPUTE v2,https://mathgen.stats.ox.ac.uk/impute/impute_v2.html; GRAIL,http://www.broadinstitute.org/mpg/grail/; DAPPLE v2,http://www.broadinstitute.org/mpg/dapple/dappleTMP.php; MAGENTA,http://www.broadinstitute.org/mpg/magenta/; Ingenuity Pathway Analysis (IPA),http://www.ingenuity.com/; AmiGO, http://geneontology.org/page/go-enrichment-analysis; European Molecular Biology Laboratory–European Bioinformatics Institute (EMBL-EBI) Immunogenetics HLA database, http://www.ebi.ac.uk/imgt/hla/; Omixon target software,http://www.omixon.com/hla/.
你这个问题很复杂,需要打赏,请点击 http://www.bio-info-trainee.com/donate 进行打赏,谢谢
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