PMC:4157143 / 29640-31437 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4157143","sourcedb":"PMC","sourceid":"4157143","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4157143","text":"Large-Effect cis-eQTLs in the Family Might Further Modify Complex-Disease-Associated Genes\nThere has been considerable interest in whether rare variants modify risk of complex disease.46,47 Although we were unable to directly test disease associations within this family because of the anonymity of the individuals, we sought to quantify the number of genome-wide association study (GWAS) genes in which cis-eQTLs exhibited larger effects in the family than in the population. We identified 315 GWAS genes in which the known GWAS variant was an eQTL in the population (at an FDR of 5%), suggesting a regulatory basis to disease pathogenesis. Of these genes, we identified 65 with a larger-effect cis-eQTL in the family (\u003e80th percentile). Of those, 17 (Table S9) were not polymorphic for the known GWAS SNP in the family, and two had a rare and potentially regulatory variant (within \u003c100 kb of the TSS, within an ENCODE TF binding and DNase I hypersensitivity peak, and with a PhyloP score \u003e 0) influencing genes implicated in body mass index, hypertension, and obesity. In addition, regardless of relative effect sizes of eQTLs between the family and population, we identified four GWAS genes (Table S10) in which the known GWAS SNP was an eQTL in the population and that had a rare and potentially regulatory variant (within \u003c100 kb of the TSS, within an ENCODE TF binding and DNase I hypersensitivity peak, and with a PhyloP score \u003e 3) in the family according to strong predictor variables. Although increased risk in this family is not known, the presence of rare and potentially regulatory variants in complex-disease-associated genes whose expression is implicated in disease pathogenesis suggests that complex traits and genes should be further studied with rare-variant association tests.","divisions":[{"label":"title","span":{"begin":0,"end":90}}],"tracks":[{"project":"2_test","denotations":[{"id":"25192044-22251874-2055647","span":{"begin":187,"end":189},"obj":"22251874"},{"id":"25192044-20479773-2055647","span":{"begin":187,"end":189},"obj":"20479773"}],"attributes":[{"subj":"25192044-22251874-2055647","pred":"source","obj":"2_test"},{"subj":"25192044-20479773-2055647","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec9396","default":true}]}]}}