Cognitive Capacity Genomewide Polygenic Scores Identify Individuals Resilient to Cognitive Decline in Aging

Abstract The genetic underpinnings of cognitive resilience in aging remains unknown. Predicting an individual’s rate of cognitive decline—or cognitive resilience—using genetics will allow personalized intervention for cognitive enhancement and optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores(GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we examined the genetic liability of cognitive abilities in the behavioral/cognitive phenome to understand individual phenotypic differences over time. We analyzed the 18-year records of the cross-sectional and longitudinal sociogenomic data of 8,511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), especially focusing on the cognitive assessments that were repeatedly administered to the participants at their average ages of 64.5 and 71.5. Our linear mixed-effects model identified a significant interaction effect between age and cognitive capacity GPS, which indicates that a higher cognitive capacity GPS significantly correlates with a slower cognitive decline in the domain of immediate memory recall (p-value = 1.79E-03, β = 1.86E-01). Also, the phenome-wide analysis identified several significant associations of cognitive capacity GPSs on the cognitive and behavioral phenome, such as Similarities task (p-value = 3.59E-74, β = 1.36, 95% CI=(1.22, 1.51)), Number Series task(p-value = 2.55E-78, β = 0.94, 95% CI=(0.85, 1.04)), IQ scores(p-value = 7.74E-179, β = 1.42, 95% CI=(1.32, 1.51)), high school class rank (p-value = 3.07E-101, β = 1.86, 95% CI=(1.69, 2.02), Openness from the BIG 5 personality factor(p-value = 2.19E-14, β = 0.57, 95% CI=(0.42, 0.71)), and social participation of reading books (p-value = 2.03E-21, β = 0.50, 95% CI=(0.40, 0.60)), attending cultural events, such as concerts, plays or museums (p-value = 2.06E-23, β = 0.60, 95% CI=(0.49, 0.72)), and watching TV (p-value = 4.16E-18, β=-0.48, 95% CI=(-0.59, -0.37)). As the first phenome-wide analysis of cognitive and behavioral phenotypes, this study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in an aging population.

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Cognitive Capacity Genomewide Polygenic Scores Identify Individuals Resilient to Cognitive Decline in Aging

10.21203/rs.3.rs-139515/v1 ◽

2021 ◽

Author(s):

Yoonjung Yoonie Joo ◽

Jiook Cha ◽

Jeremy Freese ◽

M Geoffrey Hayes

Keyword(s):

Cognitive Decline ◽

Cognitive Abilities ◽

Cognitive Capacity ◽

European Ancestry ◽

Memory Recall ◽

Protective Effects ◽

The Novel ◽

Cognitive Domains ◽

Genome Wide ◽

Polygenic Scores

Abstract The genetic underpinnings of cognitive resilience in aging remains unknown. Predicting an individual’s rate of cognitive decline—or cognitive resilience—using genetics will allow personalized intervention for cognitive enhancement and optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores(GPS) as the genomic indicators for variations of human intelligence, we examined the genetic liability of cognitive abilities in the behavioral/cognitive phenome to understand individual differences in cognitive capacity over time. Using the longitudinal sociogenomic data of 8,509 European-ancestry adults between the ages of mid-60s to 70s, we found that a higher cognitive GPS significantly correlated with a slower cognitive decline specifically in memory recall, but not in other cognitive domains. Linear mixed models with cognitive GPSs explained proportions of the variances in cognitive tests up to 60.4%. This study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in aging population.

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Do social factors mediate or moderate the sensory-cognitive associations in older adults in the Canadian Longitudinal Study on Aging?

10.31234/osf.io/y8mh9 ◽

2019 ◽

Author(s):

Anni Hämäläinen ◽

Natalie Phillips ◽

Walter Wittich ◽

Paul Mick ◽

M Kathleen Pichora-Fuller

Keyword(s):

Longitudinal Study ◽

Cognitive Decline ◽

Social Factors ◽

Pure Tone Audiometry ◽

Sensory Function ◽

Sensory Loss ◽

Protective Effects ◽

Social Variables ◽

Cross Sectional ◽

Age Related

Sensory and cognitive function both tend to decline with increasing age. Sensory impairments are risk factors for age-related cognitive decline and dementia. One hypothesis about sensory-cognitive associations is that sensory loss results in social isolation which, in turn, is a risk factor for cognitive decline. We tested whether social factors are associated with cognitive and sensory function, and whether sensory-cognitive associations are mediated or moderated by social factors. We used cross-sectional data from 30,029 participants in the Canadian Longitudinal Study of Aging, aged 45-85 years, who had no reported cognitive impairment or diagnosis of dementia. We found strong independent associations of self-reported social variables with hearing (pure-tone audiometry), vision (pinhole-corrected visual acuity), and executive function and weaker associations with memory. The moderating and mediating effects of social variables on sensory-cognitive associations were weak and mostly non-significant, but social factors could be slightly more important for females and older people. Partial retirement (relative to full retirement or not being retired) may have protective effects on cognition in the presence of hearing loss. These findings confirm the association between social factors and sensory and cognitive measures. However, support is weak for the hypothesis that social factors shape sensory-cognitive associations.

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Genome-wide Polygenic Scores for Multiple Psychiatric and Common Traits Identify Preadolescent Youth with Risk for Suicide

10.21203/rs.3.rs-136949/v2 ◽

2021 ◽

Author(s):

Yoonjung Yoonie Joo ◽

Seo-Yoon Moon ◽

Hee-Hwan Wang ◽

Hyeonjin Kim ◽

Eun-Ji Lee ◽

...

Keyword(s):

Machine Learning ◽

Suicidal Ideation ◽

Family Environment ◽

Autism Spectrum ◽

Cognitive Capacity ◽

European Ancestry ◽

Environment Interaction ◽

Genome Wide ◽

Polygenic Scores ◽

Preadolescent Youth

Abstract Importance. Suicide is the second leading cause of death in children worldwide but no available means exist to identify the risk in youth. Objective. To predict the risk of suicide in children and to investigate whether and to what extents genetic factors and a major environmental risk factor, early life stress(ELS), influence youth suicide. Design, Setting and Participants. We analyzed the genotype-phenotype data of 11,869 preadolescent children ages 9- to 10-year-old from the Adolescent Brain and Cognitive Development (ABCD) study. We estimated genome-wide polygenic scores (GPSs) of 25 complex traits to investigate their phenome-wide associations and predictive utility with suicidality (suicidal ideation and attempt) with machine learning approaches. Predictors. GPSs of 25 traits including psychiatric disorders, personality, cognitive capacity, and psychological traits. Parent Child Behavior Checklist to measure ELS in youth and Youth Family Environment Scale to assess family environment. Main outcomes and Measures. Records of suicidal ideation and attempt of the participants were derived from the computerized version of Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Results. We identified three GPSs associated with youth suicidality in multiethnic (n = 7,206) and European-ancestry (n = 5,749) participants: ADHD (P = 3.48x10− 4; odds ratio = 1.13 in multiethnic participants, P = 5.60x10− 5, OR = 1.25 in European-ancestry participants), general happiness (P = 1.43x10− 3; OR = 0.89 in multiethnic, P = 8.61x10− 4, OR = 0.89 in European) and autism spectrum disorder(ASD) (P = 1.81x10− 3; OR = 1.15 in multiethnic, P = 1.26x10− 3, OR = 1.18 in European). We also found a significant GPS-by-environment interaction between the effects of genetic risk factors for ASD and the level of ELS in increasing the risk for suicidal ideation (P = 1.36x10− 2, OR = 1.12 in multiethnic, P = 1.39x10− 3, OR = 1.19 in European). A machine learning model trained on the same data showed moderately accurate prediction of children with overall suicidal ideation with a test ROC-AUC of 0.727 (0.746 in European), and with suicidal attempts with a test ROC-AUC of 0.641 (0.975 in European) in held-out samples. Conclusions and Relevance. This study provides the first quantitative account of polygenic and environmental factors of suicidality in a large, representative population of preadolescent youth. It thus shows the potential utility of the GPSs in identifying a child with high risk for suicidality for early screening, intervention, and prevention.

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Characteristics of Cognitive Status in Sub-Population of Sub-Acute Stage of Ischemic Stroke Patients in West Nusa Tenggara, Indonesia

Kesmas National Public Health Journal ◽

10.21109/kesmas.v16i3.4297 ◽

2021 ◽

Vol 16 (3) ◽

Author(s):

Herpan Syafii Harahap ◽

Muhammad Akbar ◽

Jumraini Tammasse ◽

Andi Kurnia Bintang ◽

Andi Alfian Zainuddin

Keyword(s):

Logistic Regression ◽

Ischemic Stroke ◽

Cognitive Decline ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Cognitive Status ◽

Acute Stage ◽

P Value ◽

Stroke Patients ◽

Cross Sectional

Cognitive decline is a significant complication that affects most stroke survivors. Early detection of cognitive decline in ischemic stroke patients and identification of risk factors improves their clinical outcomes. This study aimed to determine the characteristics of cognitive status in the sub-acute phase of ischemic stroke. A cross-sectional study was conducted on 89 sub-acute ischemic stroke patients in three hospitals in West Nusa Tenggara recruited consecutively from August 2019 to April 2020. The data collected were demographic and clinical characteristics, cognitive status, and functional outcome. The association between clinical and demographic characteristics and cognitive decline was analyzed using logistic regression. In addition, the relationship between cognitive status and functional outcomes of these patients was examined using the chi-square test. This study revealed that the prevalence of cognitive decline in these subjects was 71.9%. Multiple logistic regression showed that age was the only characteristic associated with cognitive decline in the subjects (OR = 5.12,95% CI = 1.08-24.28). Furthermore, the frequency of cognitive decline in these subjects was significantly associated with functional outcomes (p-value =0.014). Thus, there was a high prevalence of cognitive decline in sub-acute ischemic stroke patients associated with increasing age and poor functional outcomes.

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Ancestry-specific polygenic scores and SNP heritability of 25(OH)D in African- and European-ancestry populations

10.1101/596619 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kathryn E. Hatchell ◽

Qionshi Lu ◽

Scott J. Hebbring ◽

Erin D. Michos ◽

Alexis C. Wood ◽

...

Keyword(s):

Vitamin D ◽

Genetic Risk ◽

Genetic Factors ◽

African Ancestry ◽

The United States ◽

Vitamin D Supplementation ◽

European Ancestry ◽

P Value ◽

Vitamin D Intake ◽

Polygenic Scores

AbstractContextVitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D levels has been discovered.ObjectiveTherefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of morbidity and mortality from deficient 25(OH)D.DesignUsing PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors.Patients or Other ParticipantsParticipants (European ancestry n=9,569, African ancestry n=2,761) came from three cohort studies.Main Outcome Measure(s)Blood concentrations of 25(OH)D.ResultsThe PGS for African ancestry was derived using all input SNPs (a p-value cut-off of 1.0) and had an R2of 0.3%; for European ancestry, the optimal PGS used a p-value cut-off of 3.5×10−4in the target/tuning dataset and had an R2of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/ml lower than those with lowest genetic risk (p=0.0463 to 3.2×10−13), requiring an additional 467 to 500 IU of vitamin D intake to maintain equivalent 25(OH)D.ConclusionsPGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.

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The Impact of Early Life Stress on the Genetic Influence on Brain and Cognitive Development in Children

10.1101/2021.12.27.21268445 ◽

2021 ◽

Author(s):

Hee-Hwan Wang ◽

Seo-Yoon Moon ◽

KaKyeong Kim ◽

Hyun-Jin Kim ◽

Woo-Young Ahn ◽

...

Keyword(s):

Cognitive Development ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Genetic Influence ◽

Cognitive Capacity ◽

European Ancestry ◽

Structural Development ◽

Polygenic Scores ◽

The Impact

Early life stress (ELS), such as abuse, neglect, and maltreatment, is a well-known risk factor for mental illness. However, it is unclear how ELS affects the brain and cognitive development. Identifying specific relationships of ELS with the genetic and brain-related underpinnings of cognitive development may reveal biological mechanisms responsible for the negative impact of ELS and those that lead to individual differences in sensitivity (or resilience) to ELS. In this study, to investigate the interlinked processes of cognitive development, we analyzed the multimodal data of DNA genotypes, brain imaging (MRI), and neuropsychological assessment (NIH Toolbox) outcomes of 4,276 children (ages 9 to 10 years, European ancestry) from the Adolescent Brain Cognitive Development (ABCD) study. We estimated the genetic influence on cognitive capacity using genome-wide polygenic scores (GPSs). Our regression and mediation analyses revealed significant causal relationships for the gene-brain-cognition pathway: Brain structural development significantly mediated the genetic influence on cognitive development (partial mediation effect = 0.016, PFWE<0.001). Interestingly, within the triangular relationship, we found a significant moderation effect of abuse only on the gene-to-brain pathway (Index of Moderated Mediation = -0.007; 95% CI= -0.012 ~ -0.002; PFWE<0.05). These findings indicate the negative modulatory effects of ELS on the genetic influence on brain structural development that lead to disadvantageous neurocognitive development in prepubertal children.

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Genetically-determined higher TSH is associated with lower risk of diabetes mellitus in individuals with low BMI

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab277 ◽

2021 ◽

Author(s):

Maxime M Bos ◽

Nicolien A van Vliet ◽

Simon P Mooijaart ◽

Raymond Noordam ◽

Diana van Heemst

Keyword(s):

Diabetes Mellitus ◽

Lower Risk ◽

European Ancestry ◽

Risk Scores ◽

P Value ◽

Protective Effects ◽

Uk Biobank ◽

Thyroid Status ◽

Low Bmi ◽

Genetically Determined

Abstract Context Thyroid status is hypothesized to be causally related with the risk of diabetes mellitus (DM), but previous results were conflicting possibly due to a complex interaction between TSH, body mass index (BMI) and DM. Objective To investigate the causal association between thyroid status with DM and glucose homeostasis and to what extent this association is dependent on BMI Design Mendelian Randomization study. Setting European-ancestry participants from the UK Biobank population. Participants The present study was performed in 408,895 individuals (mean age 57.4 years (standard deviation 8.0), 45.9% men), of which 19,773 DM cases. Interventions Genetic variants for circulatory thyroid stimulating hormone (TSH), free thyroxine (fT4) concentrations and BMI to calculate weighted genetic risk scores. Main Outcome Measures(s) self-reported DM, stratified analyses by BMI. Analyses were repeated for non-fasting glucose and Hb1Ac among individuals without DM. Results Genetically-determined TSH and fT4 levels were not associated with risk of DM in the total UK Biobank population. However, in analyses stratified on genetically-determined BMI, genetically-determined higher TSH, and not fT4, was associated with a lower risk for DM only in the low BMI group (odds ratio 0.91; 95% confidence interval 0.85,0.98 in low BMI; p-value for interaction = 0.06). Similar results were observed for glucose and Hb1Ac among individuals without DM. Conclusions TSH, but not fT4, is a potential causal risk factor for DM in individuals with genetically determined low BMI highlighting potential protective effects of TSH only in low-risk populations.

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Dietary patterns and cognitive function risk in the elderly in a county of Guangxi: a cross-sectional study

10.21203/rs.3.rs-944450/v1 ◽

2021 ◽

Author(s):

Ruoyu Gou ◽

You Li ◽

Weiyi Pang ◽

Chunbao Mo ◽

Jiansheng Cai ◽

...

Keyword(s):

Cognitive Function ◽

Protective Effect ◽

Cognitive Decline ◽

Dietary Patterns ◽

Dietary Habits ◽

The Elderly ◽

Confounding Factors ◽

Protective Effects ◽

Cross Sectional Survey ◽

Cross Sectional

Abstract Objective: To explore the effects of changes in dietary patterns on the cognitive functions of elderly people aged 60 and above in Gongcheng County. Methods: A cross-sectional survey was conducted to study the health status of the elderly population in Gongcheng County, Guangxi. A quantitative food frequency table was used in obtaining information about eating habits, and the Chinese version of the Simple Mental State Examination Scale was used in obtaining the cognitive function score. Three main dietary patterns were obtained through factor analysis, and the significance of the main dietary structure and cognitive function was analyzed through logistic regression. Results: This study covered 1246 elderly patients, of which 221 had cognitive impairments, accounting for 17.7%. Three dietary patterns were extracted. The cereal and potato dietary model and oil tea-type dietary model had no protective effects on cognitive function (P > 0.05), whereas the vegetable and fruit-based diet pattern exerted a protective effect on cognition before and after the adjustment of potential confounding factors. This protective effect alleviated decline in cognitive function (before adjustment for confounding factors: odds ratio [OR] = 2.05; 95% confidence interval [CI] = 1.34–3.15; P < 0.05; after adjustment, OR = 2.11, 95% CI = 1.34–3.33, and P < 0.05). Conclusion: Traditional dietary patterns: (grain and potato dietary models and oil-tea-type dietary patterns) cannot alleviate cognitive decline. This study suggests that a specific structure of dietary habits (vegetable and fruit-based dietary patterns) can protect the elderly against cognitive decline.

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Relationship of tooth loss to mild cognitive impairment among middle-aged Mongolians: Mon-Timeline study

Neuroscience Research Notes ◽

10.31117/neuroscirn.v4i4.88 ◽

2021 ◽

Vol 4 (4) ◽

pp. 10-18

Author(s):

Urangoo Ganbaatar ◽

Oyuntuya Gantulga ◽

Puntsagdulam Byambajav ◽

Maralgua Och ◽

Ganjargal Ganburged ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Tooth Loss ◽

Cross Sectional Study ◽

Middle Aged ◽

Significant Interaction Effect ◽

Cross Sectional ◽

Aged People ◽

Relationship Of

Cognitive impairment is common in elderly people, so it is considered an ageing disorder. However, cognitive decline, including dementia, can also occur in middle-aged people. Cognitive impairment is associated with multiple risk factors. We hypothesised that tooth loss might also be a potential risk factor among Mongolians, as oral health problems are one of the significant health issues in Mongolia, especially in middle-aged people. In this cross-sectional study, we used the baseline data from the Mon-Timeline cohort study, including people older than 40 years of age (n=279). The amount of tooth loss was assessed by a trained researcher. Mild cognitive impairment (MCI) was defined as those participants scoring a total of £ 24 points based on the Mini-Mental State Examination (MMSE). Unadjusted analysis showed that having more tooth loss (>10) increased the risk of MCI by an odds ratio of 3.03 (1.49-6.17), as compared with having less tooth loss (£10). Even after adjusting for covariates, the association remained significant, suggesting that tooth loss is associated with MCI risk, independent of age, education, and other socioeconomic factors. There was no significant interaction effect of age in the association between tooth loss and MMSE scores. In conclusion, tooth loss may play a role in developing cognitive decline, especially in the early onset of dementia. Further studies are needed to investigate whether early tooth loss at younger ages is associated with dementia, especially among middle-aged people.

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