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

for the Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 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).

Original languageEnglish (US)
Article number439
JournalBMC Genomics
Volume17
DOIs
StatePublished - Jun 29 2016

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Single Nucleotide Polymorphism
Cerebrospinal Fluid
Brain
Brain Diseases
3' Untranslated Regions
Enzymes
Growth
Brain Neoplasms
Neurodegenerative Diseases
Parkinson Disease
Meta-Analysis
prostatic acid phosphatase
Prostate
Linear Models
Neoplasms
Prostatic Neoplasms
Schizophrenia
Mental Health
Alzheimer Disease
Anxiety

Keywords

  • Brain
  • Cancer
  • CSF
  • PAP

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels. / for the Alzheimer's Disease Neuroimaging Initiative.

In: BMC Genomics, Vol. 17, 439, 29.06.2016.

Research output: Contribution to journalArticle

for the Alzheimer's Disease Neuroimaging Initiative. / Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels. In: BMC Genomics. 2016 ; Vol. 17.
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title = "Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels",
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 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).",
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AU - for the Alzheimer's Disease Neuroimaging Initiative

AU - Staley, Lyndsay A.

AU - Ebbert, Mark T W

AU - Bunker, Daniel

AU - Bailey, Matthew

AU - Weiner, Michael

AU - Aisen, Paul

AU - Petersen, Ronald

AU - Jack, Clifford R.

AU - Jagust, William

AU - Trojanowki, John Q.

AU - Toga, Arthur W.

AU - Beckett, Laurel

AU - Green, Robert C.

AU - Saykin, Andrew

AU - Morris, John

AU - Shaw, Leslie M.

AU - Ridge, Perry G.

AU - Goate, Alison M.

AU - Kauwe, John S K

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AB - 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).

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