Expressive

rs10945406 (THBS2): Alzheimer's Brain and Cognitive Traits

Key takeaways

  • rs10945406, near THBS2-AS1 and THBS2, was examined in a genome-wide scan of Alzheimer's disease brain and cognitive traits.
  • Data came from 931 Europeans assessed on MRI brain scans and memory and thinking tests in the EMIF-AD MBD study.
  • Researchers used continuous test scores rather than simple disease-versus-healthy groupings, which can improve genetic detection sensitivity.
  • Evidence is from one study with a modest sample size and should be treated as preliminary.

Key takeaways

  • rs10945406 is located near THBS2-AS1 and THBS2 and has been examined in a genome-wide scan of Alzheimer's disease-related brain imaging and cognitive performance traits.
  • Evidence comes from a single GWAS of 931 European individuals in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) cohort.
  • The study used continuous brain imaging and cognitive scores as outcomes rather than standard case-control groupings, an approach the authors proposed as more statistically sensitive.
  • The sample size is modest by GWAS standards and no replication data is reported; evidence at this locus should be treated as preliminary.

What the research says Homann et al. conducted 19 separate GWAS analyses using data from 931 participants in the EMIF-AD MBD study, examining five MRI brain imaging traits and seven neuropsychological performance measures as quantitative outcomes related to Alzheimer's disease. The study design measured each participant on continuous biological and cognitive scales - an approach called the quantitative endophenotype design - rather than grouping individuals as AD cases or healthy controls, which the authors proposed as a more powerful alternative. Longitudinal cognitive assessments covering at least two timepoints produced the most genome-wide significant signals across all 19 outcome scans in the study, and the X chromosome was included in the analysis, which is often excluded in comparable GWAS.

Reported associations

  • Alzheimer's disease-related brain imaging and cognitive phenotypes: rs10945406, at this locus, was examined across 19 quantitative GWAS outcomes in the EMIF-AD MBD cohort (n=931 European individuals); specific association statistics for this variant are not detailed in the available study data.

Evidence quality Evidence for rs10945406 comes from a single GWAS by Homann et al. (Frontiers in Aging Neuroscience, 2025) in 931 Europeans from the EMIF-AD MBD cohort. This is a small sample relative to the tens of thousands typical in large AD GWAS, limiting power to detect variants with small effects. The study's use of longitudinal neuropsychological outcomes may partially compensate by increasing sensitivity per individual. No independent replication at this locus is reported in the available data. Polygenic score analyses in the same study showed expected associations with prior hippocampal volume and cognitive function GWAS findings but not with the most recent AD risk GWAS results, suggesting the quantitative endophenotype approach may capture partially distinct biology. Overall, evidence at this locus should be treated as preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10945406?

rs10945406 is a common DNA spelling variant located near the THBS2 and THBS2-AS1 genes. It has been studied in a genome-wide association analysis of Alzheimer's disease brain imaging and cognitive performance in 931 European individuals.

Is rs10945406 associated with Alzheimer's disease?

This variant has been examined in a GWAS of Alzheimer's disease-related brain and cognitive traits. Evidence comes from a single study of 931 individuals, which means any association is preliminary until confirmed in larger or independent datasets.

What was the EMIF-AD MBD study?

The EMIF-AD MBD (European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery) study examined 931 European individuals using brain MRI scans and neuropsychological tests as continuous genetic outcome measures, rather than a standard case-versus-control design.

Why did this study use brain scans and memory tests instead of a standard Alzheimer's diagnosis?

The researchers used continuous biological and cognitive measurements, called quantitative endophenotypes, rather than a binary disease label. This approach can capture more information about how traits vary between people and may improve statistical sensitivity for finding genetic associations.