Search results for "rare variants"
showing 3 items of 3 documents
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
2018
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 ca…
Exome sequencing of three cases of familial exceptional longevity
2014
Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Inter…