@article{e45657aabd0a47b491220257001acbc8,
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).",
keywords = "Brain, CSF, Cancer, PAP",
author = "{for the Alzheimer's Disease Neuroimaging Initiative} and Staley, {Lyndsay A.} and Ebbert, {Mark T.W.} and Daniel Bunker and Matthew Bailey and Michael Weiner and Paul Aisen and Ronald Petersen and Jack, {Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and Saykin, {Andrew J.} and John Morris and Shaw, {Leslie M.} and Ridge, {Perry G.} and Goate, {Alison M.} and Kauwe, {John S.K.}",
note = "Funding Information: The authors acknowledge that many scientists contributed in developing theclinical and genetic resources necessary to collect these data and completethis project. The authors also gratefully acknowledge the efforts of hundredsof individuals who participated as subjects in these studies.The NIH (R01 AG035053, R01 AG042611, P50 AG05681, P01 AG03991, P01AG026276), the Alzheimer's Association (MNIRG-11-205368), and the BrighamYoung University Gerontology Program provided support for this work. Wealso acknowledge the Alzheimer's Disease Genetics Consortium (ADGC) andGenetic and Environmental Risk for Alzheimer's Disease Consortium (GERAD)for providing genotype data used in this work. GERAD was supported by theMedical Research Council (Grant nu 503480), Alzheimer's Research UK (Grantnu 503176), the Wellcome Trust (Grant nu 082604/2/07/Z) and GermanFederal Ministry of Education and Research (BMBF): Competence NetworkDementia (CND) grant nu 01GI0102, 01GI0711, 01GI0420. CHARGE was partlysupported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 andAGES contract N01-AG-12100, the NHLBI grant R01 HL105756, the IcelandicHeart Association, and the Erasmus Medical Center and Erasmus University.ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886,U01 AG016976, and the Alzheimer's Association grant ADGC-10-196728.Data collection and sharing for this project was funded by the Alzheimer'sDisease Neuroimaging Initiative (ADNI) (National Institutes of Health GrantU01 AG024904) and DOD ADNI (Department of Defense award numberW81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, theNational Institute of Biomedical Imaging and Bioengineering, and throughgenerous contributions from the following: Alzheimer's Association; Alzheimer'sDrug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-MyersSquibb Company; Eisai Inc.; ElanPharmaceuticals, Inc.; Eli Lilly and Company; F.Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare;Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research and Development, LLC.; Johnson Johnson Pharmaceutical Research DevelopmentLLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.;NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging;Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The CanadianInstitutes of Health Research is providing funds to support ADNI clinical sites inCanada. Private sector contributions are facilitated by the Foundation for theNational Institutes of Health (www.fnih.org). The grantee organization is theNorthern California Institute for Research and Education, and the study is coordinatedby the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. Some of the samples used inthis study were genotyped by the ADGC and GERAD. ADGC is supported bygrants from the NIH (#U01AG032984) and GERAD from the Wellcome Trust(GR082604MA) and the Medical Research Council (G0300429).Portions of data used in preparation of this article were obtained from theAlzheimer's Disease Neuroimaging Initiative (ADNI) database(adni.loni.usc.edu). As such, the investigators within the ADNI contributed tothe design and implementation of ADNI and/or provided data but did notparticipate in analysis or writing of this report.The ADNI Executive Committee consists of: Michael Weiner, MD UC SanFrancisco; Paul Aisen, MD UC San Diego; Ronald Petersen, MD, PhD MayoClinic, Rochester; Clifford R. Jack, Jr., MD Mayo Clinic, Rochester; WilliamJagust, MD UC Berkeley; John Q. Trojanowki, MD, PhD U Pennsylvania; ArthurW. Toga, PhD USC; Laurel Beckett, PhD UC Davis; Robert C. Green, MD, MPHBrigham and Women's Hospital/Harvard Medical School; Andrew J. Saykin,PsyD Indiana University; John Morris, MD Washington University St. Louis;Leslie M. Shaw University of Pennsylvania. A complete listing of ADNIinvestigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf Publisher Copyright: {\textcopyright} 2016 The Author(s).",
year = "2016",
month = jun,
day = "29",
doi = "10.1186/s12864-016-2787-y",
language = "English (US)",
volume = "17",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
}