rs10514413 (ADAMTS18): Alzheimer's Endophenotype Variant

Key takeaways

• rs10514413 near ADAMTS18 was studied in a genome-wide scan of early Alzheimer's biological markers.
• The study tracked brain volume, memory test scores, and spinal fluid proteins in people who were cognitively normal or mildly impaired.
• Sample sizes ranged from about 300 to 580 per analysis group, making findings preliminary.
• No lifestyle or medication associations have been reported for this variant in the available evidence.

What the research says rs10514413, near the ADAMTS18 gene, was evaluated in a genome-wide association study (GWAS - a method that scans the entire genome for genetic variants linked to measurable traits) of Alzheimer's disease (AD) endophenotypes (measurable biological indicators of the disease that can be tracked before dementia develops). The study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multisite research program that follows participants across three cognitive stages: cognitively normal (CN), mild cognitive impairment (MCI - a stage with modest memory changes not meeting dementia criteria), and AD dementia. Endophenotypes analyzed included hippocampal volume (HPV - the size of a brain region central to memory), logical memory test scores (verbal recall performance), and cerebrospinal fluid (CSF) levels of amyloid-beta 42 and tau proteins, which are chemical markers associated with AD. Specific association results for rs10514413 were not detailed in the available study excerpt.

Reported associations

• Alzheimer's disease endophenotypes: rs10514413 was examined in relation to hippocampal volume, verbal memory performance, and CSF levels of amyloid-beta 42, total tau (t-Tau), and phosphorylated tau (p-Tau) in ADNI participants stratified by cognitive stage, in a 2019 GWAS by Chung et al. published in Alzheimer's and Dementia.

Evidence quality The source study enrolled approximately 1,189 ADNI participants before quality control across two genotyping arrays (ADNI-1 and ADNI-GO/2). After quality control, the CN subgroup included 305 individuals (ADNI-1: 187; ADNI-GO/2: 118) and the MCI subgroup included 581 individuals (ADNI-1: 329; ADNI-GO/2: 252). The study-wide significance threshold was P less than 8.3 x 10-9. The study's primary reported significant associations were for t-Tau near SRRM4 and C14orf79, hippocampal volume near MTUS1 (both in CN subjects), and logical memory delayed recall near ZNF804B (in MCI subjects); these are distinct loci from ADAMTS18. These are modest sample sizes for a GWAS, and single-cohort findings at this scale are considered preliminary until replicated in independent populations. Specific effect sizes and p-values for this variant are not reported in the available excerpt, and replication status is not described.

Lifestyle considerations No lifestyle considerations on file for this variant.