Interpreting Gene Expression Effects of Disease-Associated Variants: A Lesson from <i>SNCA</i> rs356168.

ABSTRACT: The SNCA intronic single nucleotide polymorphism (SNP), rs356168, has been associated with Parkinson's disease (PD) in large genome wide association studies (GWAS). Recently, the PD-risk allele, rs356168-G was shown to increase SNCA-mRNA expression using genome edited human induced pluripotent stem cells (iPSC)-derived neurons. In this study, as means of validation, we tested the effect of rs356168 on total SNCA-mRNA levels using brain tissues, temporal and frontal cortex, from healthy control donors. Carriers of the rs356168-G allele demonstrated a borderline significant decrease of SNCA-mRNA levels in temporal brain tissues (p = 0.02) compared to individuals homozygous for the 'A' allele. Similar trend, but weak, was observed in the analysis of frontal

SUBMITTER: Glenn OC 

PROVIDER: S-EPMC5611418 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature