Genome-wide association study identified ATP6V1H locus influencing cerebrospinal fluid BACE activity

BMC Med Genet. 2018 May 11;19(1):75. doi: 10.1186/s12881-018-0603-z.

Abstract

Background: The activity of cerebrospinal fluid (CSF) β-site APP cleaving enzyme (BACE) is a potential diagnostic biomarker for Alzheimer disease (AD).

Methods: A total of 340 non-Hispanic Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI) database were included in this study with quality-controlled CSF BACE and genotype data. Association of CSF BACE with the genetic variants of single nucleotide polymorphisms (SNPs) was assessed using PLINK under the additive genetic model. The P values of all SNPs for CSF BACE were adjusted for multiple comparisons.

Results: One SNP (rs1481950) in the ATP6V1H gene reached genome-wide significance for associations with CSF BACE (P = 4.88 × 10- 9). The minor allele (G) of rs1481950 was associated with higher CSF BACE activity. Although seven SNPs in SNX31, RORA, CDH23, RGS20, LRRC4C, MAPK6PS1 and LOC105378355 did not reach genome-wide significance (P < 10- 8), they were identified as suggestive loci (P < 10- 5).

Conclusion: This study identified rs1481950 within ATP6V1H influencing human CSF BACE activity, which indicated that ATP6V1H gene may play some roles in the pathogenesis of neurodegenerative diseases such as AD.

Keywords: ADNI; ATP6V1H; Alzheimer’s disease; BACE.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Amyloid Precursor Protein Secretases / cerebrospinal fluid*
  • Aspartic Acid Endopeptidases / cerebrospinal fluid*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Vacuolar Proton-Translocating ATPases / genetics*

Substances

  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • ATP6V1H protein, human
  • Vacuolar Proton-Translocating ATPases