rs11929485 (CASR): Memory Genetics and Gene Expression

Key takeaways

• rs11929485 sits in the CASR - HNRNPA1P23 region and was part of one of the largest sex-stratified memory genetics studies to date, covering more than 27,000 older adults.
• The study drew on four cognitive aging cohorts and included both non-Hispanic White and non-Hispanic Black participants to improve generalizability.
• Tissue expression data from GTEx show the ALT allele increases FAM162A activity in the pancreas and reduces KPNA1 activity in skeletal muscle.
• Specific effect sizes for this variant on memory are not available in the provided research, so evidence should be treated as preliminary.

What the research says A sex-stratified genome-wide association study (GWAS - a method that scans hundreds of thousands of genetic positions across the genome simultaneously) of late-life memory enrolled 11,942 males and 15,641 females across four cognitive aging cohorts - the Adult Changes in Thought study, the Alzheimer's Disease Neuroimaging Initiative, and the Religious Orders Study/Memory and Aging Project/Minority Aging Research Study - including non-Hispanic White (n = 24,216) and non-Hispanic Black (n = 3,367) participants, with rs11929485 among the variants examined. The study applied harmonized composite memory scores to improve comparability across cohorts and tested both sex-stratified and sex-interaction models to detect genetic effects that may differ between males and females. Separately, GTEx v11 tissue expression data (953 donors, cis-window eQTL analysis, FDR < 0.05) show that the ALT allele of rs11929485 is associated with higher FAM162A expression in pancreatic tissue (slope +0.28, p = 5.4e-5) and lower KPNA1 expression in skeletal muscle (slope -0.14, p = 7.6e-5) GTEx Portal.

Reported associations

• Late-life memory performance: rs11929485 was captured in a sex-stratified GWAS of memory performance in older adults (N = 27,583 total: 11,942 males, 15,641 females); specific association statistics for this variant are not detailed in the available study excerpt.
• FAM162A gene expression - pancreas: The ALT allele is associated with increased FAM162A expression in pancreatic tissue (slope +0.28, p = 5.4e-5) GTEx Portal.
• KPNA1 gene expression - skeletal muscle: The ALT allele is associated with reduced KPNA1 expression in skeletal muscle (slope -0.14, p = 7.6e-5) GTEx Portal.

Evidence quality The memory GWAS is among the largest sex-aware genetic studies of late-life memory conducted to date, with a combined sample of 27,583 participants drawn from four well-characterized cohorts and covering both non-Hispanic White and non-Hispanic Black ancestry groups, which improves generalizability relative to single-ancestry studies. The study explicitly named three genome-wide significant, sex-specific loci in its primary findings (rs67099044, rs719070, rs5935633); rs11929485 is not among those highlighted, indicating its memory association - if present - may fall below standard genome-wide significance thresholds (typically p < 5e-8) or appear only in supplementary analyses. No p-value, effect size, or replication status specific to this variant's memory association is available from the provided text. The GTEx eQTL (expression quantitative trait locus) evidence for the FAM162A and KPNA1 expression effects is based on 953 donors across tissues at FDR < 0.05 and represents mechanistic, expression-level data distinct from any clinical outcome evidence.

Tissue-specific expression effects

• FAM162A: The ALT allele is linked to increased expression in pancreatic tissue GTEx Portal.
• KPNA1: The ALT allele is linked to reduced expression in skeletal muscle GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.