rs11019328 (LINC02748): Genetic Variant Evidence

Key takeaways

• No direct association for rs11019328 was reported in either of the two genome-wide studies reviewed.
• A GWAS of cognitive resilience to Alzheimer's disease (n = 5,024) and a metabolic GWAS in elite athletes (n = 490) were reviewed.
• The Alzheimer's resilience study found cognitive resilience to be 20-25% heritable and identified a distinct female-specific locus at rs827389 on chromosome 10.
• The elite athlete study tested 275,016 variants and reported novel associations at the FOLH1 and VNN1 loci, not at this variant.
• Evidence quality for rs11019328 cannot be assessed from the provided study excerpts.

What the research says Two genome-wide association studies were reviewed for information on rs11019328. A sex-stratified GWAS of cognitive resilience to Alzheimer's disease neuropathology enrolled 5,024 participants (2,093 males, 2,931 females) and estimated resilience heritability at 20-25% across both sexes combined, with sex-specific estimates ranging from 15-44%. A separate metabolic GWAS in 490 elite athletes tested 275,016 SNPs (single-nucleotide polymorphisms, meaning single-letter differences in the DNA code) against 751 serum metabolite profiles and identified novel variant-metabolite associations at the FOLH1 and VNN1 loci. Neither study's available text contains a direct report of findings for rs11019328 in the LINC02748 region.

Reported associations

• Cognitive resilience to Alzheimer's disease (lead locus rs827389, not rs11019328): In the sex-stratified GWAS, the variant rs827389 on chromosome 10 was associated with higher resilience scores specifically in females (beta = 0.08, p = 5.76 x 10^-9 in females, n = 2,931), with no detectable effect in males (beta = -0.01, p = 0.70, n = 2,093). The sex-interaction term was also significant (beta = 0.09, p = 1.01 x 10^-4). The rs827389 locus lies within chromatin loops (structural DNA folding that brings distant genomic regions into contact) that interact with promoters of genes involved in RNA processing, including GATA3. No association was reported for rs11019328 in the available text.
• Elite athlete metabolite profiles: In 490 elite athletes, novel variant-metabolite associations were reported at FOLH1 (linked to N-acetyl-aspartyl-glutamate, a compound involved in neurotransmitter signaling), VNN1 (linked to Linoleoyl ethanolamide, a fatty acid derivative), and SULT2A1 (linked to androstenediol monosulfate, a steroid-related compound, specifically in endurance athletes). A meta-analysis across two cohorts confirmed 104 metabolites associated with endurance sport level. No association was reported for rs11019328 in the available text.

Evidence quality The provided study excerpts do not contain direct evidence for rs11019328 associations. The cognitive resilience GWAS (Eissman et al., 2022, Brain) was a well-powered sex-stratified analysis harmonizing continuous cognitive phenotypes across four cohorts and autopsy amyloid measures across two cohorts, representing a methodologically rigorous design. The metabolic GWAS (Al-Khelaifi et al., 2020, Scientific Reports) was the first reported mQTL study in elite athletes and was exploratory in nature; its sample size of 490 is small by GWAS standards, and the authors note that replication is needed. Neither study's available text addresses rs11019328, so evidence quality for this specific variant remains undetermined from these excerpts alone.

Lifestyle considerations No lifestyle considerations on file for this variant.