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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0603-z) contains supplementary material, which is available to authorized users.