scholarly journals MEF2C Common Genetic Variation Is Associated With Different Aspects of Cognition in Non-Hispanic White and Caribbean Hispanic Non-demented Older Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
Preeti Sunderaraman ◽  
Stephanie Cosentino ◽  
Nicole Schupf ◽  
Jennifer Manly ◽  
Yian Gu ◽  
...  
Keyword(s):  
Older Adults ◽  
Ethnic Groups ◽  
Processing Speed ◽  
Nucleotide Polymorphisms ◽  
Association Analyses ◽  
Cognitive Domains ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Washington Heights ◽  
Hispanic White

ObjectivesMyocyte Enhancer Factor 2C (MEF2C) is identified as a candidate gene contributing to the risk of developing Alzheimer’s disease. However, little is known about whether MEF2C plays a role in specific aspects of cognition among older adults. The current study investigated the association of common variants in the MEF2C gene with four cognitive domains including memory, visuospatial functioning, processing speed and language among non-demented individuals.MethodParticipants from two ethnic groups, Non-Hispanic White (NHW; n = 537) and Caribbean Hispanic (CH; n = 1,197) from the Washington Heights-Inwood Community Aging Project (WHICAP) study, were included. Genetic association analyses using WHICAP imputed genome-wide data (GWAS) were conducted for the various cognition domains.ResultsSingle nucleotide polymorphisms (SNP) variants in the MEF2C gene showed nominally significant associations in all cognitive domains but for different SNPs across both the ethnic groups. In NHW participants, the strongest associations were present for memory (rs302484), language (rs619584), processing speed (rs13159808), and visuospatial functioning (several SNPs). In CH, strongest associations were observed for memory (rs34822815), processing speed (rs304141), visuospatial functioning (rs10066711 and rs10038371), and language (rs304153).DiscussionMEF2C variant-cognitive associations shed light on an apparent role for MEF2C in both memory and non-memory aspects of cognition in individuals from NHW and CH ancestries. However, the little overlap in the specific SNP-cognition associations in CH versus NHW highlights the differences in genetic architectural variations among those from different ancestries that should be considered while studying the MEF2C gene.

scholarly journals Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 686
Author(s):  
Alireza Nazarian ◽  
Alexander M. Kulminski
Keyword(s):  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Significance Level ◽  
Association Analyses ◽  
Complex Disorders ◽  
Specific Effects ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Sex Disparities ◽  
Almost All

Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at P < 5.0 × 10−6 neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.

scholarly journals Genotyping-by-Sequencing of Gossypium hirsutum Races and Cultivars Uncovers Novel Patterns of Genetic Relationships and Domestication Footprints

2019 ◽  
Vol 15 ◽  
pp. 117693431988994
Author(s):  
Shulin Zhang ◽  
Yaling Cai ◽  
Jinggong Guo ◽  
Kun Li ◽  
Renhai Peng ◽  
...  
Keyword(s):  
Gossypium Hirsutum ◽  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
Genotyping By Sequencing ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Breeding Programs ◽  
Association Analyses ◽  
Genome Wide ◽  
Candidate Gene Locus

Determining the genetic rearrangement and domestication footprints in Gossypium hirsutum cultivars and primitive race genotypes are essential for effective gene conservation efforts and the development of advanced breeding molecular markers for marker-assisted breeding. In this study, 94 accessions representing the 7 primitive races of G hirsutum, along with 9 G hirsutum and 12 Gossypium barbadense cultivated accessions were evaluated. The genotyping-by-sequencing (GBS) approach was employed and 146 558 single nucleotide polymorphisms (SNP) were generated. Distinct SNP signatures were identified through the combination of selection scans and association analyses. Phylogenetic analyses were also conducted, and we concluded that the Latifolium, Richmondi, and Marie-Galante race accessions were more genetically related to the G hirsutum cultivars and tend to cluster together. Fifty-four outlier SNP loci were identified by selection-scan analysis, and 3 SNPs were located in genes related to the processes of plant responding to stress conditions and confirmed through further genome-wide signals of marker-phenotype association analysis, which indicate a clear selection signature for such trait. These results identified useful candidate gene locus for cotton breeding programs.

scholarly journals Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study

2016 ◽  
Vol 47 (5) ◽  
pp. 971-980 ◽  
Author(s):  
S. H. Gage ◽  
H. J. Jones ◽  
S. Burgess ◽  
J. Bowden ◽  
G. Davey Smith ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Positive Control ◽  
Negative Control ◽  
Study Data ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Genome Wide Data

BackgroundObservational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data.MethodWe performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10−5) and schizophrenia (p < 5 × 10−8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses.ResultsThere was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01–1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05–1.14, p = 2.64 × 10−5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99–1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97–1.00, p = 0.066) analyses.ConclusionsOur results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.

scholarly journals The influence of X chromosome variants on trait neuroticism

2018 ◽  
Author(s):  
Michelle Luciano ◽  
Gail Davies ◽  
Kim M Summers ◽  
W David Hill ◽  
Caroline Hayward ◽  
...  
Keyword(s):  
X Chromosome ◽  
Nucleotide Polymorphisms ◽  
Nucleic Acid Binding ◽  
Single Nucleotide ◽  
Association Analyses ◽  
Complex Disorders ◽  
Genome Wide ◽  
Intergenic Regions ◽  
Protein Classes ◽  
Sample Maximum

Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately-powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of these significant neuroticism-related X chromosome variants were located in intergenic regions (n = 713). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.34% (SE = 0.07). A polygenic X-variant score created in an independent sample (maximum N ≈ 7300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.

scholarly journals SNP-SNP interactions as risk factors for aggressive prostate cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 621 ◽  
Author(s):  
Venkatesh Vaidyanathan ◽  
Vijay Naidu ◽  
Nishi Karunasinghe ◽  
Anower Jabed ◽  
Radha Pallati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
New Zealand ◽  
Nucleotide Polymorphisms ◽  
Aggressive Prostate Cancer ◽  
Association Analyses ◽  
Male Health ◽  
Genome Wide ◽  
Strong Candidate ◽  
Gene X Environment Interactions

Prostate cancer (PCa) is one of the most significant male health concerns worldwide. Single nucleotide polymorphisms (SNPs) are becoming increasingly strong candidate biomarkers for identifying susceptibility to PCa. We identified a number of SNPs reported in genome-wide association analyses (GWAS) as risk factors for aggressive PCa in various European populations, and then defined SNP-SNP interactions, using PLINK software, with nucleic acid samples from a New Zealand cohort. We used this approach to find a gene x environment marker for aggressive PCa, as although statistically gene x environment interactions can be adjusted for, it is highly impossible in practicality, and thus must be incorporated in the search for a reliable biomarker for PCa. We found two intronic SNPs statistically significantly interacting with each other as a risk for aggressive prostate cancer on being compared to healthy controls in a New Zealand population.

Candidate-gene association study searching for genetic factors involved in migraine chronification

Cephalalgia ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 500-507 ◽  
Author(s):  
MA Louter ◽  
J Fernandez-Morales ◽  
B de Vries ◽  
B Winsvold ◽  
V Anttila ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Factors ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Candidate Gene Association ◽  
Genome Wide ◽  
Third Stage ◽  
Genome Wide Data ◽  
Two Stages

Introduction Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. Methods We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. Results Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. Discussion We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification.

Heterogeneity of late-life depression: relationship with cognitive functioning

2014 ◽  
Vol 26 (6) ◽  
pp. 953-963 ◽  
Author(s):  
Nicole C. M. Korten ◽  
Brenda W. J. H. Penninx ◽  
Rob M. Kok ◽  
Max L. Stek ◽  
Richard C. Oude Voshaar ◽  
...  
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Functioning ◽  
Psychotropic Medication ◽  
Processing Speed ◽  
Depressive Episode ◽  
Late Life ◽  
Late Life Depression ◽  
Symptom Dimensions ◽  
Cognitive Domains

ABSTRACTBackground:Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains.Methods:Cross-sectional data of 378 depressed and 132 non-depressed older adults between 60–93 years, from the Netherlands Study of Depression in Older adults (NESDO) were used. Depressed older adults were recruited from both inpatient and outpatient mental healthcare institutes and general practices, and diagnosed according to DSM-IV-TR criteria. Multivariable associations were examined with depression characteristics (severity, onset, comorbidity, psychotropic medication) and symptom dimensions as independent variables and cognitive domains (episodic memory, processing speed, interference control, working memory) as dependent variables.Results:Late-life depression was associated with poorer cognitive functioning. Within depressed participants, higher severity of psychopathology and having a first depressive episode was associated with poorer cognitive functioning. The use of tricyclic antidepressants, serotonergic and noradrenergic working antidepressants, and benzodiazepines was associated with worse cognitive functioning. Higher scores on the mood dimension were associated with poorer working memory and processing speed, whereas higher scores on a motivational and apathy dimension were associated with poorer episodic memory and processing speed.Conclusions:Heterogeneity in late-life depression may lead to differences in cognitive functioning. Higher severity and having a first depressive episode was associated with worse cognitive performance. Additionally, different domains of cognitive functioning were associated with specific symptom dimensions. Our findings on the use of psychotropic medication suggest that close monitoring on cognitive side effects is needed.

scholarly journals Plasma Long Chain Fatty Acids and Cognitive Function in Older Adults: A Comparison of Statistical Analyses

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 13-13
Author(s):  
Caroline Duchaine ◽  
Pierre-Hugues Carmichael ◽  
Nancy Presse ◽  
Alexandra Fiocco ◽  
Pierrette Gaudreau ◽  
...  
Keyword(s):  
Older Adults ◽  
Fatty Acids ◽  
Cognitive Function ◽  
Sex Education ◽  
Processing Speed ◽  
Verbal Memory ◽  
Successful Aging ◽  
Omega 3 ◽  
Cognitive Domains ◽  
Long Chain

Abstract Omega-3 fatty acids (FAs) have been suggested as modifiable protective factors for cognitive decline because of their neuroprotective properties. However, the evidence is still inconsistent regarding types of omega-3 FAs, and the probable interrelation with other circulating long chain FAs (LCFAs). This study aimed to evaluate associations between 14 plasma LCFAs and four cognitive domains using a principal component analysis (PCA) and to compare results with those obtained using standard methods. A group of 386 healthy older adults aged 77 ± 4 years (53% women), selected from the NutCog Study, a sub-study from the Québec cohort on Nutrition and Successful Aging (NuAge), underwent a cognitive evaluation and fasting blood sampling. Verbal and non-verbal episodic memory, executive functioning, and processing speed were evaluated using validated tests. LCFAs circulating concentrations were measured by high-performance liquid chromatography using published procedures. Linear regressions adjusted for age, sex, education, and BMI were used to evaluate cross-sectional associations between LCFAs, using PCA or a more standard grouping (omega-3, omega-6, monounsaturated, and saturated LCFAs), and cognitive performance. Higher scoring on the omega-3 PCA factor and higher concentrations of total omega-3 FAs were both associated with better episodic non-verbal memory and processing speed. Higher eicosapentaenoic acid (EPA omega-3) was also associated with these two cognitive domains and with episodic verbal memory. The associations with total omega-3 FAs taken separately were of smaller magnitude than those with PCA. These results suggest that omega-3 FAs should be considered in combination with other LCFAs when evaluating the association with cognitive function.

Abstract 17111: Genetic Influences on Human Plasma Metabolites That Determine Mortality in Heart Failure Patients

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
David E Lanfear ◽  
Hongsheng Gui ◽  
Jia Li ◽  
Ruicong She ◽  
Edward Peterson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Strong Association ◽  
Plasma Metabolites ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Association Analyses ◽  
Reduced Ejection Fraction ◽  
Genome Wide ◽  
Plasma Metabolite

Background: Heart failure with reduced ejection fraction (HFrEF) continues to be a global health burden. We recently reported a strong association of plasma metabolite profile (thirteen different metabolites) with survival among patients with HFrEF but the mechanism of this association is unclear. We studied the genetic associations of plasma metabolite to try to illuminate the disease mechanisms at work. Methods: A prospective genetic registry including 1032 HFrEF with genome-wide genotyping and imputation of single nucleotide polymorphisms (SNP; ~7 millions) and targeted metabolomics profiling. Genome-wide (GW) association analyses were performed to investigate the genetic impact of each SNP on the 13 metabolites of interest. Analyses were performed using linear models stratified by race (European Americans [N=516] and African Americans [N=516] and including the top five principal components (PC) for each population to avoid spurious associations due to population stratification. A fixed-effect meta-analysis was then used to combine results from the two populations. Threshold for GW significance was p<5E-8. As a second step, Cox proportional hazard regression models of overall survival were tested for each SNP that met GW significance. Results: We found at least one SNP reaching GW significance for 6 metabolites metabolites (a-KG, C5.Isovaleryl, Fumarate, Leucine, Succinate and X3.HBA). The most significant SNP (rs77836784, an intronic variant within PACRG) was associated with X3.HBA in African American HF patients (Beta estimate=22.82, P-value=7.14E-14). A cross-checking of SNP associations on both metabolites and HF survival identified 13 independent SNPs that may partially explain the contribution of the metabolites on HF mortality (Table 1) and seem to have biologic plausibility including for example a G-protein coupled receptor (GPR68) and protein kinase C (PRKC1). Conclusion: Genetic variants are associated with predictive plasma metabolites and survival. This may be useful to understand the underlying pathways connecting metabolites to HF progression. A complete investigation of genomic and metabolomics determinants including causal mediation and pathway analyses are on-going.

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