Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels

BMC Genomics. 2016 Jun 29;17 Suppl 3(Suppl 3):439. doi: 10.1186/s12864-016-2787-y.


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 of p < 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 underlie ACPP 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).

Keywords: Brain; CSF; Cancer; PAP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid Phosphatase / cerebrospinal fluid*
  • Acid Phosphatase / genetics*
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics
  • Brain / enzymology
  • Brain / metabolism
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Frequency
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Linear Models
  • Meta-Analysis as Topic*
  • Middle Aged
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / genetics
  • Polymorphism, Single Nucleotide*
  • Risk Factors


  • Acid Phosphatase
  • prostatic acid phosphatase