rs114350689 (LINC01121): Sex-Specific Memory Variant
Key takeaways
- rs114350689 sits near LINC01121, a regulatory RNA gene that does not produce a protein
- Identified in the largest sex-aware genetic study of late-life memory to date, covering roughly 27,000 older adults
- Memory heritability is comparable across sexes, but specific genetic drivers including this locus may differ between men and women
- The study examined the genetic basis of a documented pattern: women outscore men on memory tests when healthy, but lose that edge in Alzheimer's disease
Key takeaways
- rs114350689 sits near LINC01121, a regulatory RNA gene that does not produce a protein
- Identified in the largest sex-aware genetic study of late-life memory to date, covering roughly 27,000 older adults
- Memory heritability is comparable across sexes, but specific genetic drivers including this locus may differ between men and women
- The study examined the genetic basis of a documented pattern: women outscore men on memory tests when healthy, but lose that edge in Alzheimer's disease
What the research says A sex-stratified and sex-interaction genome-wide association study (GWAS - a method that scans the entire genome for DNA variants linked to a trait) of late-life memory performance was conducted across four cohorts of cognitive aging and Alzheimer's disease research, enrolling approximately 27,000 participants (11,942 males, 15,641 females), including 24,216 non-Hispanic White and 3,367 non-Hispanic Black individuals. Harmonized memory composite scores - a standardized measurement approach applied consistently across all cohorts - were used to reduce differences in how memory was measured between studies. The analysis identified sex-specific genetic loci (chromosomal locations), including the LINC01121 locus, along with heparan sulfate signaling as a sex-specific pathway and sex-specific shared genetic architecture between memory and cardiovascular, immune, and educational traits.
Reported associations
- Late-life memory performance: rs114350689 near LINC01121 was identified in a sex-stratified GWAS of late-life memory performance across approximately 27,000 older adults drawn from cognitive aging and Alzheimer's disease cohorts
- Sex-specific memory genetics: The analysis found that while the heritable component of late-life memory is broadly comparable across sexes, specific variants at loci including this one may have effects that differ between men and women
Evidence quality This study is described by its authors as the largest sex-aware GWAS of late-life memory to date, with approximately 27,000 participants (N males = 11,942; N females = 15,641) across four cohorts. Inclusion of both non-Hispanic White (n = 24,216) and non-Hispanic Black (n = 3,367) participants adds cross-ancestry breadth. Harmonized memory composite scores reduce measurement heterogeneity across cohorts, strengthening cross-study comparability. However, specific p-values, effect sizes, or sex-specific directionality for rs114350689 are not present in the available study text. This variant was not among the three top-highlighted loci named in the study abstract (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP1, and rs5935633-EGL6/TCEANC/OFD1), which suggests it may represent a secondary or subthreshold finding rather than a genome-wide significant hit. Replication of this specific locus in independent samples is not addressed in the provided text, so the evidence should be considered preliminary.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is LINC01121?
LINC01121 is a long intergenic non-coding RNA - a gene that produces an RNA molecule rather than a protein. These regulatory molecules are thought to influence how other genes are switched on or off, though the specific role of LINC01121 is still under investigation.
What does rs114350689 do?
rs114350689 is a single-letter DNA change located near LINC01121. It was flagged in a large sex-stratified genetic study of late-life memory, suggesting it may contribute to sex-specific differences in how genetics influences memory performance in older adults. Specific effect sizes are not yet available in published summaries.
Is rs114350689 linked to Alzheimer's disease?
This variant was identified in a study that recruited participants from Alzheimer's disease cohorts and used memory test scores as the outcome. The study did not directly test for an association with an Alzheimer's disease diagnosis, so no direct causal link to the disease has been established from the available evidence.
Why does genetics affect memory differently in men and women?
Women tend to perform better on verbal and episodic memory tasks when cognitively healthy, but this gap narrows with Alzheimer's disease. Sex-stratified genetic analyses look for variants whose effect on memory scores differs between men and women, pointing to biological pathways that operate differently across sexes. The full picture remains under active investigation.
How strong is the evidence for rs114350689?
The study it comes from is large, covering roughly 27,000 participants with harmonized measurements across four cohorts. However, specific effect sizes and significance thresholds for this variant were not available in the published text reviewed here, and it was not among the top-highlighted findings, so the evidence should be treated as preliminary until independently replicated.