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APOE Genotype-Stratified Meta-Analysis of Cognitive Decline Reveals Novel Loci for Language and Global Cognitive Function in Older Adults

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: APOE Genotype-Stratified Meta-Analysis of Cognitive Decline Reveals Novel Loci for Language and Global Cognitive Function in Older Adults
Συγγραφείς: Vibha Acharya, Kang-Hsien Fan, Beth E. Snitz, Mary Ganguli, Steven T. DeKosky, Oscar L. Lopez, Eleanor Feingold, M. Ilyas Kamboh
Πηγή: International Journal of Molecular Sciences ; Volume 26 ; Issue 14 ; Pages: 6940
Στοιχεία εκδότη: Multidisciplinary Digital Publishing Institute
Έτος έκδοσης: 2025
Συλλογή: MDPI Open Access Publishing
Θεματικοί όροι: APOE -stratified, genome-wide association, neurocognitive domains, attention, visuospatial function, memory, executive function, language, global cognitive function
Περιγραφή: Apolipoprotein E (APOE) allele 4 (APOE4), one of the robust genetic risk factors for AD, has also been associated with cognitive decline in terms of memory, executive function, language, and global cognitive function. APOE genotype-stratified analysis can help to identify additional genetic loci which might be masked due to a strong effect of APOE4. We conducted a genome-wide meta-analysis in APOE2 carriers, APOE4 carriers, and APOE 3/3 homozygote groups among 2969 non-Hispanic Whites aged ≥ 65 years using slopes of decline over time across five cognitive domains (attention, language, executive function, memory, and visuospatial function) and global cognitive function. We identified novel genome-wide significant associations for decline in global cognitive function in the intergenic region between RNU7-66P/RNA5SP208 at rs116379916 (p = 1.44 × 10−9) in the APOE 3/3 group and for decline in language in the intergenic region between LINC0221/DTWD2 at rs13187183 (p = 3.79 × 10−8) in APOE4 carriers. A previously reported locus for decline in attention near RASEF at rs6559700 (p = 9.95 × 10−9) was found to be confined to the APOE 3/3 group. We also found two sub-threshold significant associations in the APOE 2 group for decline in attention (IL1RL2/rs77127114; p = 8.64 × 10−8) and decline in language (YTHDC2/KCNN2, rs116191836; p = 5.66 × 10−8). Our study points to potential biological pathways pertaining to specific domains within each APOE genotype group, and the findings suggest that immune-related pathways, plasma levels of polysaturated fatty acids, and bitter taste receptors may play roles in cognitive decline. Our findings enhance the understanding of cognitive aging and provide a framework for future studies.
Τύπος εγγράφου: Thesis
Περιγραφή αρχείου: application/pdf
Γλώσσα: English
Relation: Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms26146940
DOI: 10.3390/ijms26146940
Διαθεσιμότητα: https://doi.org/10.3390/ijms26146940
Rights: https://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.D1DDB9B2
Βάση Δεδομένων: BASE
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  – Url: https://doi.org/10.3390/ijms26146940#
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  Data: APOE Genotype-Stratified Meta-Analysis of Cognitive Decline Reveals Novel Loci for Language and Global Cognitive Function in Older Adults
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  Data: <searchLink fieldCode="AR" term="%22Vibha+Acharya%22">Vibha Acharya</searchLink><br /><searchLink fieldCode="AR" term="%22Kang-Hsien+Fan%22">Kang-Hsien Fan</searchLink><br /><searchLink fieldCode="AR" term="%22Beth+E%2E+Snitz%22">Beth E. Snitz</searchLink><br /><searchLink fieldCode="AR" term="%22Mary+Ganguli%22">Mary Ganguli</searchLink><br /><searchLink fieldCode="AR" term="%22Steven+T%2E+DeKosky%22">Steven T. DeKosky</searchLink><br /><searchLink fieldCode="AR" term="%22Oscar+L%2E+Lopez%22">Oscar L. Lopez</searchLink><br /><searchLink fieldCode="AR" term="%22Eleanor+Feingold%22">Eleanor Feingold</searchLink><br /><searchLink fieldCode="AR" term="%22M%2E+Ilyas+Kamboh%22">M. Ilyas Kamboh</searchLink>
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  Data: International Journal of Molecular Sciences ; Volume 26 ; Issue 14 ; Pages: 6940
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  Data: Multidisciplinary Digital Publishing Institute
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  Data: 2025
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  Data: MDPI Open Access Publishing
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  Data: <searchLink fieldCode="DE" term="%22APOE+-stratified%22">APOE -stratified</searchLink><br /><searchLink fieldCode="DE" term="%22genome-wide+association%22">genome-wide association</searchLink><br /><searchLink fieldCode="DE" term="%22neurocognitive+domains%22">neurocognitive domains</searchLink><br /><searchLink fieldCode="DE" term="%22attention%22">attention</searchLink><br /><searchLink fieldCode="DE" term="%22visuospatial+function%22">visuospatial function</searchLink><br /><searchLink fieldCode="DE" term="%22memory%22">memory</searchLink><br /><searchLink fieldCode="DE" term="%22executive+function%22">executive function</searchLink><br /><searchLink fieldCode="DE" term="%22language%22">language</searchLink><br /><searchLink fieldCode="DE" term="%22global+cognitive+function%22">global cognitive function</searchLink>
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  Data: Apolipoprotein E (APOE) allele 4 (APOE4), one of the robust genetic risk factors for AD, has also been associated with cognitive decline in terms of memory, executive function, language, and global cognitive function. APOE genotype-stratified analysis can help to identify additional genetic loci which might be masked due to a strong effect of APOE4. We conducted a genome-wide meta-analysis in APOE2 carriers, APOE4 carriers, and APOE 3/3 homozygote groups among 2969 non-Hispanic Whites aged ≥ 65 years using slopes of decline over time across five cognitive domains (attention, language, executive function, memory, and visuospatial function) and global cognitive function. We identified novel genome-wide significant associations for decline in global cognitive function in the intergenic region between RNU7-66P/RNA5SP208 at rs116379916 (p = 1.44 × 10−9) in the APOE 3/3 group and for decline in language in the intergenic region between LINC0221/DTWD2 at rs13187183 (p = 3.79 × 10−8) in APOE4 carriers. A previously reported locus for decline in attention near RASEF at rs6559700 (p = 9.95 × 10−9) was found to be confined to the APOE 3/3 group. We also found two sub-threshold significant associations in the APOE 2 group for decline in attention (IL1RL2/rs77127114; p = 8.64 × 10−8) and decline in language (YTHDC2/KCNN2, rs116191836; p = 5.66 × 10−8). Our study points to potential biological pathways pertaining to specific domains within each APOE genotype group, and the findings suggest that immune-related pathways, plasma levels of polysaturated fatty acids, and bitter taste receptors may play roles in cognitive decline. Our findings enhance the understanding of cognitive aging and provide a framework for future studies.
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  Data: Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms26146940
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  Data: 10.3390/ijms26146940
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  Data: https://doi.org/10.3390/ijms26146940
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      – SubjectFull: APOE -stratified
        Type: general
      – SubjectFull: genome-wide association
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      – SubjectFull: neurocognitive domains
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            – TitleFull: International Journal of Molecular Sciences ; Volume 26 ; Issue 14 ; Pages: 6940
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