Dataset Information

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

ABSTRACT: APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes.

SUBMITTER: Granot-Hershkovitz E

PROVIDER: S-EPMC10060219 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

Granot-Hershkovitz Einat E Xia Rui R Yang Yunju Y Spitzer Brian B Tarraf Wassim W Vásquez Priscilla M PM Lipton Richard B RB Daviglus Martha M Argos Maria M Cai Jianwen J Kaplan Robert R Fornage Myriam M DeCarli Charles C Gonzalez Hector M HM Sofer Tamar T

Scientific reports 20230329 1

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry ...[more]

PMID: 36991100

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Project description:BackgroundThe relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos.ObjectiveTo understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos.MethodsParticipants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol).ResultsCentral obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =-0.165, p < 0.001) and to more pronounced cognitive declines over the average 7 years (ΔGlobalCognition = -0.109, p < 0.05); this was consistent across cognitive domains.ConclusionCentral obesity alone was not associated with cognitive function. However, presence of both central obesity and cardiometabolic abnormalities was robustly predictive of cognition and 7-year cognitive declines, suggesting that in combination these factors may alter the cognitive trajectories of middle-aged and older Hispanics/Latinos.

Project description:Objective: The effects of normal cognitive aging on executive functions (EF), Verbal Episodic Memory (VEM) and the contribution of age, sex, education, and APOΕ ε4 in a group of old Greek Cypriots across a five-year period were investigated. Design: NEUROAGE, the first project on cognitive aging in Cyprus, is a prospective longitudinal study with a rolling admission process. Participants are assessed at baseline and retested every 24-30 months. Subjects: 170 participants completed all three testing cycles; 86 men and 84 women with ages ranging between 60 and 88 years (mean = 73.21, SD = 5.84); education, 2-20 years (mean = 9.07, SD = 4.27). Results: Α Repeated Measures Multivariate Analysis of Covariance was conducted with one between-subject factor: sex; two covariates: age and education, while Time (time 1, time 2, time 3) served as a within - subject factor. Time did not have an effect on mini mental status examination in Greek (MMSE), EF or VEM. Also, sex had no effect on MMSE, EF and VEM. There was no time by sex interaction. Age and Education significantly predicted the EF performance, F(1, 168) = 11.23, p < 0.05; F(1, 158) = 90.03, p < 0.001 and VEM performance, F(1, 171) = 17.22, p < 0.001; F(1, 171) = 61.25, p < 0.001. Furthermore, there was a significant interaction effect between time and education, for EF, F(2, 167) = 7.02, p < 0.001. Performance of the APOE ε4 carriers did not differ on any of the above measures as compared to performance of non-carriers in this older adult group. Conclusion: Cognitively healthy adults maintained overall cognitive performance across the five-year period. Male and female participants performed similarly and the pattern of change over time was similar across the two sexes. Education was predictive of VEM and EF performance across time. Furthermore, those with higher education maintained higher levels of EF performance. APOE results did not differentiate performance at baseline. Implications of findings are discussed.

Dataset Information

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

Publications

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

Similar Datasets

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