title: Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels.
abstract: 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.
  
  
  
  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.
  
  
  
  Thirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlie ACPP regulation and expression.
  
  
  
  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).
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Lyndsay A
authors.initials: LA
authors.lastname: Staley
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Mark T W
authors.initials: MT
authors.lastname: Ebbert
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bunker
authors.affiliation: Biology and Biomedical Sciences, Washington University, St. Louis, MO, 63110, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Perry G
authors.initials: PG
authors.lastname: Ridge
authors.affiliation: Department of Neuroscience Icahn School of Medicine, New York, NY, 10029, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA. Kauwe@byu.edu.
authors.forename: John S K
authors.initials: JS
authors.lastname: Kauwe
mesh_terms: D000135:Acid Phosphatase / Q000134:cerebrospinal fluid* / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D016014:Linear Models; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000135:Acid Phosphatase; C428439:prostatic acid phosphatase
keywords: Brain; CSF; Cancer; PAP