Expression Quantitative Trait Loci for ALMS1 and Their Influence on the Symptoms of Alstrom Syndrome

Abstract

Genome-wide expression quantitative trait loci (eQTL) were identified for ALMS1, which is known as a causal gene for Alstrom syndrome. Genetic associations of nucleotide variants were examined with expression of the gene encoding ALMS] in lymphoblastoid cell lines derived from 373 Europeans. The analyses revealed six cis-regulatory eQTLs for ALMS] (P <5 x 10(-8) ), showing a strong signal (P <10(-20)) upstream of the gene. Transcriptomewide association analysis with these eQTLs revealed that 16 genes shared eQTLs with ALMS] (P <1.02 x 10(-4)). These genes included MOCS3, CDH3, Clorf100, CXCL14, CDK4, and PCBD1, which are involved in the symptoms of Alstrom syndrome. This study suggested six novel eQTLs for ALMS1 and their associations with 16 additional genes. The candidate genes whose expressions were associated with eQTL for ALMS1 might directly or indirectly cause symptoms of Alstrom syndrome. Further studies are required to understand their underlying regulatory mechanisms of the eQTLs to improve our understanding of the function of ALMS1 and other causal genes for Alstrom syndrome.