BackgroundProstatic 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.MethodsWe 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.ResultsThirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlie ACPP regulation and expression.ConclusionsGiven 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).

BackgroundCCL16 is a chemokine predominantly expressed in the liver, but is also found in the blood and brain, and is known to play important roles in immune response and angiogenesis. Little is known about the gene’s regulation.MethodsHere, we test for potential causal SNPs that affect CCL16 protein levels in both blood plasma and cerebrospinal fluid in a genome-wide association study across two datasets. We then use METAL to performed meta-analyses with a significance threshold of p < 5x10−8. We removed SNPs where the direction of the effect was different between the two datasets.ResultsWe identify 10 SNPs associated with increased CCL16 protein levels in both biological fluids.ConclusionsOur results will help understand CCL16’s regulation, allowing researchers to better understand the gene’s effects on human health.

BackgroundProlactin is a polypeptide hormone secreted by the anterior pituitary gland that plays an essential role in lactation, tissue growth, and suppressing apoptosis to increase cell survival. Prolactin serves as a key player in many life-critical processes, including immune system and reproduction. Prolactin is also found in multiple fluids throughout the body, including plasma and cerebrospinal fluid (CSF).MethodsIn this study, we measured prolactin levels in both plasma and CSF, and performed a genome-wide association study. 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.ResultsWe identified 12 SNPs associated with increased prolactin levels in both biological fluids.ConclusionsOur efforts will help researchers understand how prolactin is regulated in both CSF and plasma, which could be beneficial in research for the immune system and reproduction.

BackgroundAlzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer’s disease, including Presenilin 1 (PSEN1). Multiple studies have attempted to locate novel variants in the PSEN1 gene that affect Alzheimer's disease status. A recent study suggested that one of these variants, PSEN1 E318G (rs17125721), significantly affects Alzheimer's disease status in a large case–control dataset, particularly in connection with the APOEε4 allele.MethodsOur study looks at the same variant in the Cache County Study on Memory and Aging, a large population-based dataset. We tested for association between E318G genotype and Alzheimer’s disease status by running a series of Fisher’s exact tests. We also performed logistic regression to test for an additive effect of E318G genotype on Alzheimer’s disease status and for the existence of an interaction between E318G and APOEε4.ResultsIn our Fisher’s exact test, it appeared that APOEε4 carriers with an E318G allele have slightly higher risk for AD than those without the allele (3.3 vs. 3.8); however, the 95 % confidence intervals of those estimates overlapped completely, indicating non-significance. Our logistic regression model found a positive but non-significant main effect for E318G (p = 0.895). The interaction term between E318G and APOEε4 was also non-significant (p = 0.689).ConclusionsOur findings do not provide significant support for E318G as a risk factor for AD in APOEε4 carriers. Our calculations indicated that the overall sample used in the logistic regression models was adequately powered to detect the sort of effect sizes observed previously. However, the power analyses of our Fisher’s exact tests indicate that our partitioned data was underpowered, particularly in regards to the low number of E318G carriers, both AD cases and controls, in the Cache county dataset. Thus, the differences in types of datasets used may help to explain the difference in effect magnitudes seen. Analyses in additional case–control datasets will be required to understand fully the effect of E318G on Alzheimer's disease status.

BackgroundProstatic 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.MethodsWe 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.ResultsThirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlie ACPP regulation and expression.ConclusionsGiven 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).

BackgroundCCL16 is a chemokine predominantly expressed in the liver, but is also found in the blood and brain, and is known to play important roles in immune response and angiogenesis. Little is known about the gene’s regulation.MethodsHere, we test for potential causal SNPs that affect CCL16 protein levels in both blood plasma and cerebrospinal fluid in a genome-wide association study across two datasets. We then use METAL to performed meta-analyses with a significance threshold of p < 5x10−8. We removed SNPs where the direction of the effect was different between the two datasets.ResultsWe identify 10 SNPs associated with increased CCL16 protein levels in both biological fluids.ConclusionsOur results will help understand CCL16’s regulation, allowing researchers to better understand the gene’s effects on human health.