Expressive

rs116267766 (LYST): Memory Decline GWAS Variant

Key takeaways

  • rs116267766 is located near LYST and LINC02768, and was studied in a genome-wide scan of late-life memory in over 27,000 people.
  • The study covered both non-Hispanic White and non-Hispanic Black participants, making it one of the more ancestry-diverse memory GWAS to date.
  • The alternate allele at this locus is linked to reduced LYST gene expression in tibial artery tissue.
  • Memory performance shares genetic architecture with Alzheimer's disease, neuropsychiatric traits, and autoimmune conditions.
  • Specific effect size data for this variant on memory outcomes are not yet reported in the available evidence.

Key takeaways

  • rs116267766 is located near LYST and LINC02768, and was studied in a genome-wide scan of late-life memory in over 27,000 people.
  • The study covered both non-Hispanic White and non-Hispanic Black participants, making it one of the more ancestry-diverse memory GWAS to date.
  • The alternate allele at this locus is linked to reduced LYST gene expression in tibial artery tissue.
  • Memory performance shares genetic architecture with Alzheimer's disease, neuropsychiatric traits, and autoimmune conditions.
  • Specific effect size data for this variant on memory outcomes are not yet reported in the available evidence.

What the research says rs116267766, in the LYST-LINC02768 region, was examined in a cross-ancestry genome-wide association study (GWAS) on late-life memory performance (n = 27,633) and longitudinal memory decline (n = 22,365; 129,201 observations), drawing on harmonized cognitive data from four aging cohorts: the Adult Changes in Thought (ACT), Alzheimer's Disease Neuroimaging Initiative (ADNI), National Alzheimer's Coordinating Center (NACC), and Religious Orders Study / Rush Memory and Aging Project / Minority Aging Research Study (ROS/MAP/MARS). That work found high heritability for memory performance across ancestry groups and demonstrated that the genetic architecture of memory overlaps with that of Alzheimer's disease (AD), neuropsychiatric traits, and autoimmune traits. Independently, tissue expression data from GTEx show that the alternate allele at this locus is associated with reduced LYST expression in tibial artery tissue GTEx Portal.

Reported associations

  • Late-life memory performance: The locus was examined in a GWAS using harmonized memory performance scores across four aging cohorts (n = 27,633), including non-Hispanic White (n = 24,216) and non-Hispanic Black (n = 3,417) participants.
  • Longitudinal memory decline: The same study analyzed memory decline trajectories (n = 22,365; 129,201 longitudinal observations).
  • LYST expression in tibial artery: The alternate allele is associated with reduced expression at this locus in tibial artery tissue (slope = -0.29, p = 1.4e-5) GTEx Portal.

Evidence quality The GWAS examining this locus enrolled 27,633 participants for cross-sectional memory performance and 22,365 for longitudinal memory decline, placing it among the largest such studies conducted to date. The design incorporated harmonized phenotyping across four well-characterized aging cohorts and included two ancestry groups, which strengthens generalizability. However, the specific association statistics for rs116267766 - including effect size and p-value on memory outcomes - are not reported in the available study text; the genome-wide significant loci named in that publication are distinct variants (rs6848524 on chromosome 4, rs111471504 on chromosome 2, rs4142249 on chromosome 7, and rs74381744 on chromosome 15). The evidence linking this specific variant to memory outcomes should therefore be considered preliminary. The eQTL result for LYST in tibial artery derives from GTEx v11 (953 donors, FDR < 0.05), a well-powered multi-tissue reference dataset GTEx Portal.

Tissue-specific expression effects

  • LYST: The alternate allele is associated with reduced expression in tibial artery tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs116267766?

rs116267766 is a genetic variant near the LYST gene and a long non-coding RNA called LINC02768. It has been examined in research on late-life memory performance and decline, which are early markers linked to Alzheimer's disease.

Is rs116267766 linked to Alzheimer's disease?

This variant was studied in the context of a GWAS on memory performance, which the study authors describe as a strong endophenotype (biological marker) for Alzheimer's disease. The study found that memory genetics broadly overlap with Alzheimer's genetics, but a specific Alzheimer's diagnosis association for this variant was not reported.

How large was the study that examined this variant?

The genome-wide association study included 27,633 participants for memory performance and 22,365 for longitudinal memory decline, drawing from four major aging cohorts across the Alzheimer's Disease Sequencing Project.

What does the GTEx eQTL result for LYST mean?

The GTEx result shows that people carrying the alternate allele tend to have lower LYST gene expression in tibial artery tissue. This is a tissue-level gene expression finding, not a direct clinical outcome, and is best understood as a potential clue to the biological mechanism at this locus.

Why is memory performance used in Alzheimer's genetics research?

Memory performance is considered a strong endophenotype for Alzheimer's disease, meaning it reflects underlying biology that may be closer to the disease's genetic causes than a clinical diagnosis alone. Studying memory genetically can help identify molecular pathways relevant to Alzheimer's risk and resilience.