Whole-exome sequencing reveals common and rare variants in immunologic and neurological genes implicated in achalasia.

ABSTRACT: Idiopathic achalasia (IA) is a severe motility disorder characterized by neuronal degeneration in the myenteric plexus, but the etiology remains largely unknown. We performed whole-exome sequencing (WES) in 100 IA-affected individuals and 313 non-IA control subjects and validated the results in 230 IA-affected individuals and 1,760 non-IA control subjects. Common missense variants rs1705003 (CUTA, GenBank: NC_000006.11:g.33385953A>G) and rs1126511 (HLA-DPB1, GenBank: NC_000006.11:g.33048466G>T) at 6p21.32 were reproducibly associated with increased risk of IA (rs1126511: OR = 1.83, p = 2.34 × 10^-9; rs1705003: OR = 2.37, p = 3.21 × 10^-7), meeting exome-wide significance. Both variants can affect the expression of their target genes at the transcript level. An array-bas

SUBMITTER: Li Q 

PROVIDER: S-EPMC8387277 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature