Crohn Disease study with SNP/CNV Genotypes (NGS), Targeted-Capture data on dbGaP (763 participants)

phs001751 — Rare Disease Susceptibility Variants in Children with Crohn's Disease.

<p>We performed targeted, massively-parallel sequencing of 101 genes in 205 children with Crohn's disease, including 179 parent-child trios and 200 controls, both of European ancestry. We identified three genes with nominally significant p-values: NOD2, RTKN2, and MGAT3. Only NOD2 was significant after correcting for multiple comparisons. We identified eight novel rare variants in NOD2 that are likely disease-associated. Incorporation of rare variation and compound heterozygosity nominally increased the proportion of variance explained from 0.074 to 0.089. We estimated the population attributable risk and total heritability of variation in NOD2 to be 32.9% and 3.4%, respectively, with 3.7% and 0.25% accounted for by rare putatively functional variants. Sequencing probands (as opposed to genotyping) to identify rare variants and incorporating phase by sequencing parents can recover a portion of the missing heritability of Crohn's disease. </p> <p>(Reprinted from G3 2018;8(9): 2881-2888; PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=30166421">30166421</a>. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (<a href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</a> ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)</p>