Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels. (June 2016)

• Record Type: Journal Article
• Authors: Staley, Lyndsay; Ebbert, Mark; Bunker, Daniel; Bailey, Matthew; Ridge, Perry; Goate, Alison; Kauwe, John
• Is Part Of: BMC genomics. Volume 17:Number 3(2016)
• Page Start: 301
• Page End: 307
• Publication Date: 2016-06
• Subjects: Brain -- Cancer -- CSF -- PAP; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-2787-y
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background Prostatic Acid Phosphatase (PAP) is an enzyme that is produced primarily in the prostate and functions as a cell growth regulator and potential tumor suppressor. Understanding the genetic regulation of this enzyme is important because PAP plays an important role in prostate cancer and is expressed in other tissues such as the brain. Methods We tested association between 5.8 M SNPs and PAP levels in cerebrospinal fluid across 543 individuals in two datasets using linear regression. We then performed meta-analyses using METAL =with a significance threshold ofp < 5 × 10−8 and removed SNPs where the direction of the effect was different between the two datasets, identifying 289 candidate SNPs that affect PAP cerebrospinal fluid levels. We analyzed each of these SNPs individually and prioritized SNPs that had biologically meaningful functional annotations in wANNOVAR (e.g. non-synonymous, stop gain, 3' UTR, etc.) or had a RegulomeDB score less than 3. Results Thirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlieACPP regulation and expression. Conclusions Given PAP's expression in the brain and its role as a cell-growth regulator and tumor suppressor, our results have important implications in brain health such as cancer and other brain diseases including neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease) and mental health (e.g., anxiety, depression, and schizophrenia).