Genotype-Tissue Expression Project (GTEx)

Roadmap Epigenomics Project

這個研究的思路是什麽？鑒定出有功能調控作用的變異。

對於復雜性狀，通常會由很多遺傳因素來控制，從而影響到表型。GWAS鑒定出了很多SNP，但是卻只能解釋部分heritability。

怎麽鑒定帶有一定effect size的causal的變異來解釋缺失的heritability是現在的研究熱點。大白話就是現在的GWAS只關註 pvalue < 5x10^-8 的SNP，但這些SNP只能解釋很小一部分的遺傳性，現在普遍認為缺失的那部分就是pvalue略小的SNP中。

這些SNP大部分都坐落在非編碼區，覆蓋了大量的基因調控元件，說明這些causal SNPs是通過影響基因表達來影響表型的。

Identifying causal variants with moderate effect size underlying the missing heritability is currently one of the biggest challenges

The majority of GWAS risk loci, as well as loci with subgenome-wide significance (P values between 1 × 10−5 and 5 × 10−8), localize to non-coding genomic regions with many gene regulatory signals [3], suggesting that most trait/disease causal SNPs exert their phenotypic effects by altering gene expression

另一個證據就是這些SNPs會富集在eQTL和開放染色質區域。

This is further supported by GWAS risk loci being enriched in genomic regions with many expression quantitative trait loci (eQTLs) and open chromatins

基因調控具有高度的tissues and celltypes特異性。

variant變異 | Epigenome表觀基因組 | Disease-susceptible gene 疾病易感基因