scholarly journals Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment

2021 ◽  
pp. 1-11
Author(s):  
Jeremy Harper ◽  
Mengzhen Liu ◽  
Stephen M. Malone ◽  
Matt McGue ◽  
William G. Iacono ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Principal Component ◽  
Oscillatory Activity ◽  
Future Research ◽  
Nonparametric Bootstrap ◽  
Psychological Traits ◽  
Negatively Associated ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Band Limited

Abstract Background To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment. Method A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis. Results Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (β = −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β = −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003–0.058). Conclusions Evidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.

scholarly journals Educational Attainment and Personality Are Genetically Intertwined

2017 ◽  
Vol 28 (11) ◽  
pp. 1631-1639 ◽  
Author(s):  
René Mõttus ◽  
Anu Realo ◽  
Uku Vainik ◽  
Jüri Allik ◽  
Tõnu Esko
Keyword(s):  
Educational Attainment ◽  
Personality Traits ◽  
Personality Trait ◽  
Factor Model ◽  
Five Factor Model ◽  
Molecular Genetic ◽  
Maximum Amount ◽  
Biological Processes ◽  
Psychological Traits ◽  
Polygenic Scores

Heritable variance in psychological traits may reflect genetic and biological processes that are not necessarily specific to these particular traits but pertain to a broader range of phenotypes. We tested the possibility that the personality domains of the five-factor model and their 30 facets, as rated by people themselves and their knowledgeable informants, reflect polygenic influences that have been previously associated with educational attainment. In a sample of more than 3,000 adult Estonians, education polygenic scores (EPSs), which are interpretable as estimates of molecular-genetic propensity for education, were correlated with various personality traits, particularly from the neuroticism and openness domains. The correlations of personality traits with phenotypic educational attainment closely mirrored their correlations with EPS. Moreover, EPS predicted an aggregate personality trait tailored to capture the maximum amount of variance in educational attainment almost as strongly as it predicted the attainment itself. We discuss possible interpretations and implications of these findings.

scholarly journals Phenotypic Annotation: Using Polygenic Scores to Translate Discoveries From Genome-Wide Association Studies From the Top Down

2019 ◽  
Vol 28 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Daniel W. Belsky ◽  
K. Paige Harden
Keyword(s):  
Educational Attainment ◽  
Association Studies ◽  
Science Research ◽  
Well Being ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Research Activities ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Methodological Considerations

Genome-wide association studies (GWASs) have identified specific genetic variants associated with complex human traits and behaviors, such as educational attainment, mental disorders, and personality. However, small effect sizes for individual variants, uncertainty regarding the biological function of discovered genotypes, and potential “outside-the-skin” environmental mechanisms leave a translational gulf between GWAS results and scientific understanding that will improve human health and well-being. We propose a set of social, behavioral, and brain-science research activities that map discovered genotypes to neural, developmental, and social mechanisms and call this research program phenotypic annotation. Phenotypic annotation involves (a) elaborating the nomological network surrounding discovered genotypes, (b) shifting focus from individual genes to whole genomes, and (c) testing how discovered genotypes affect life-span development. Phenotypic-annotation research is already advancing the understanding of GWAS discoveries for educational attainment and schizophrenia. We review examples and discuss methodological considerations for psychologists taking up the phenotypic-annotation approach.

scholarly journals Genetic Association Study of Childhood Aggression across raters, instruments and age

2019 ◽  
Author(s):  
Hill F. Ip ◽  
Camiel M. van der Laan ◽  
Eva M. L. Krapohl ◽  
Isabell Brikell ◽  
Cristina Sánchez-Mora ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Genetic Correlations ◽  
Childhood Aggression ◽  
Age At First Birth ◽  
Nucleotide Polymorphisms ◽  
Obsessive Compulsive ◽  
Psychological Traits ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
Polygenic Scores

AbstractBackgroundHuman aggressive behavior (AGG) has a substantial genetic component. Here we present a large genome-wide association meta-analysis (GWAMA) of childhood AGG.MethodsWe analyzed assessments of AGG for a total of 328,935 observations from 87,485 children (aged 1.5 – 18 years), from multiple assessors, instruments, and ages, while accounting for sample overlap. We performed an overall analysis and meta-analyzed subsets of the data within rater, instrument, and age.ResultsHeritability based on the overall meta-analysis (AGGall) that could be attributed to Single Nucleotide Polymorphisms (SNPs) was 3.31% (SE=0.0038). No single SNP reached genome-wide significance, but gene-based analysis returned three significant genes: ST3GAL3 (P=1.6E-06), PCDH7 (P=2.0E-06) and IPO13 (P=2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children and in retrospectively assessed childhood aggression. We obtained moderate-to-strong genetic correlations (rg‘s) with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19 –.1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg =∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg|: 0.46 – 0.60). Genetic correlations between AGG and psychiatric disorders were strongest for mother- and self-reported AGG.ConclusionsThe current GWAMA of childhood aggression provides a powerful tool to interrogate the genetic etiology of AGG by creating individual polygenic scores and genetic correlations with psychiatric traits.

scholarly journals Educational attainment and personality are genetically intertwined

2016 ◽  
Author(s):  
René Mõttus ◽  
Anu Realo ◽  
Uku Vainik ◽  
Jüri Allik ◽  
Tõnu Esko
Keyword(s):  
Educational Attainment ◽  
Personality Traits ◽  
Personality Trait ◽  
Factor Model ◽  
Five Factor Model ◽  
Molecular Genetic ◽  
Maximum Amount ◽  
Biological Processes ◽  
Psychological Traits ◽  
Polygenic Scores

AbstractHeritable variance in psychological traits may reflect genetic and biological processes that are not necessarily specific to these particular traits but pertain to a broader range of phenotypes. We tested the possibility that Five-Factor Model personality domains and their 30 facets, as rated by people themselves and their knowledgeable informants, reflect polygenic influences that have been previously associated with educational attainment. In a sample of over 3,000 adult Estonians, polygenic scores for educational attainment (EPS; interpretable as estimates of molecular genetic propensity for education) were correlated with various personality traits, particularly from the Neuroticism and Openness domains. The correlations of personality traits with phenotypic educational attainment closely mirrored their correlations with EPS. Moreover, EPS predicted an aggregate personality trait tailored to capture maximum amount of variance in educational attainment almost as strongly as it predicted the attainment itself. We discuss possible interpretations and implications of these findings.

scholarly journals Genome-Wide Association Analyses of Fertility Traits in Beef Heifers

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 217
Author(s):  
Morgan R. Stegemiller ◽  
Gordon K. Murdoch ◽  
Troy N. Rowan ◽  
Kimberly M. Davenport ◽  
Gabrielle M. Becker ◽  
...  
Keyword(s):  
Mixed Model ◽  
Association Studies ◽  
Principal Component ◽  
Genome Wide Association ◽  
Trend Test ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Chromosome 2 ◽  
Beef Heifers ◽  
Genome Wide

The ability of livestock to reproduce efficiently is critical to the sustainability of animal agriculture. Antral follicle count (AFC) and reproductive tract scores (RTS) can be used to estimate fertility in beef heifers, but the genetic mechanisms influencing variation in these measures are not well understood. Two genome-wide association studies (GWAS) were conducted to identify the significant loci associated with these traits. In total, 293 crossbred beef heifers were genotyped on the Bovine GGP 50K chip and genotypes were imputed to 836,121 markers. A GWAS was performed with the AFC phenotype for 217 heifers with a multi-locus mixed model, conducted using the year, age at time of sampling and principal component analysis groupings as the covariates. The RTS GWAS was performed with 289 heifers using an additive correlation/trend test comparing prepubertal to pubertal heifers. The loci on chromosomes 2, 3 and 23 were significant in the AFC GWAS and the loci on chromosomes 2, 8, 10 and 11 were significant in the RTS GWAS. The significant region on chromosome 2 was similar between both analyses. These regions contained genes associated with cell proliferation, transcription, apoptosis and development. This study proposes candidate genes for beef cattle fertility, although future research is needed to elucidate the precise mechanisms.

Social and Genetic Pathways in Multigenerational Transmission of Educational Attainment

2018 ◽  
Vol 83 (2) ◽  
pp. 278-304 ◽  
Author(s):  
Hexuan Liu
Keyword(s):  
Educational Attainment ◽  
Social Environment ◽  
Genetic Effects ◽  
Genome Wide ◽  
Heart Study ◽  
Polygenic Scores ◽  
The Social ◽  
Genome Wide Data ◽  
Retirement Study ◽  
Parents Education

This study investigates the complex roles of the social environment and genes in the multigenerational transmission of educational attainment. Drawing on genome-wide data and educational attainment measures from the Framingham Heart Study (FHS) and the Health and Retirement Study (HRS), I conduct polygenic score analyses to examine genetic confounding in the estimation of parents’ and grandparents’ influences on their children’s and grandchildren’s educational attainment. I also examine social genetic effects (i.e., genetic effects that operate through the social environment) in the transmission of educational attainment across three generations. Two-generation analyses produce three important findings. First, about one-fifth of the parent-child association in education reflects genetic inheritance. Second, up to half of the association between parents’ polygenic scores and children’s education is mediated by parents’ education. Third, about one-third of the association between children’s polygenic scores and their educational attainment is attributable to parents’ genotypes and education. Three-generation analyses suggest that genetic confounding on the estimate of the direct effect of grandparents’ education on grandchildren’s education (net of parents’ education) may be inconsequential, and I find no evidence that grandparents’ genotypes significantly influence grandchildren’s education through non-biological pathways. The three-generation results are suggestive, and the results may change when different samples are used.

scholarly journals Do Low Polygenic Scores Buffer the Effects of Maltreatment? A Polygene-Environment Interaction Study of ADHD

2021 ◽  
Author(s):  
Quanfa He ◽  
James Janford Li
Keyword(s):  
Genome Wide Association Study ◽  
Alternative Methods ◽  
Future Research ◽  
Environment Interaction ◽  
Adult Health ◽  
Adhd Symptoms ◽  
Social Emotional ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Psychiatric Outcomes

Objective: This study explored whether maltreatment moderates the association of polygenic risk for ADHD. Because individuals with low polygenic scores (PGS) for ADHD were previously shown to have better than expected functional outcomes (i.e., cognitive, mental health, social-emotional) than individuals with middle or high ADHD PGS, we hypothesized that low ADHD PGS may possible confer a protective effect against maltreatment in the development of ADHD. Method: Data were from participants with phenotypic and genotypic data in the National Longitudinal Study of Adolescent to Adult Health (Add Health; n=4,722), which was used to examine the effects of ADHD PGS, maltreatment, and their interaction on childhood ADHD symptoms. ADHD PGS were generated from the most recent genome-wide association study on ADHD and categorized into three groups (i.e., low, medium, high) using empirically determined cut-points. A maltreatment factor score was derived from five forms of self-reported maltreatment experiences prior to age 18. Results: ADHD PGS and maltreatment were positively associated with ADHD symptoms, as expected. However, we did not detect an interaction between ADHD PGS and maltreatment on ADHD symptoms. Conclusion: Despite the increase in predictive power afforded by PGS, the lack of an interaction between ADHD PGS and maltreatment on ADHD symptoms converges with an emerging body of psychiatric PGS studies that have also failed to detect polygenic-environment interplay on psychiatric outcomes. We discuss possible reasons for this pattern of results and offer alternative methods for future research in revealing important polygenic-environment interactions for ADHD.

scholarly journals Molecular genetic contributions to self-rated health

2015 ◽  
Author(s):  
Sarah E Harris ◽  
Saskia P Hagenaars ◽  
Gail Davies ◽  
William David Hill ◽  
David CM Liewald ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genome Wide Association Study ◽  
Uk Biobank ◽  
Psychological Traits ◽  
Self Rated Health ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Polygenic Scores

Abstract Background Poorer self-rated health (SRH) predicts worse health outcomes, even when adjusted for objective measures of disease at time of rating. Twin studies indicate SRH has a heritability of up to 60% and that its genetic architecture may overlap with that of personality and cognition. Methods We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were used to estimate the proportion of variance explained by all common autosomal SNPs for SRH. Linkage Disequilibrium (LD) score regression and polygenic risk scoring, two complementary methods, were used to investigate pleiotropy between SRH in UK Biobank and up to 21 health-related and personality and cognitive traits from published GWAS consortia. Results The GWAS identified 13 independent signals associated with SRH, including several in regions previously associated with diseases or disease-related traits. The strongest signal was on chromosome 2 (rs2360675, p = 1.77x10-10) close to KLF7, which has previously been associated with obesity and type 2 diabetes. A second strong peak was identified on chromosome 6 in the major histocompatibility region (rs76380179, p = 6.15x10-10). The proportion of variance in SRH that was explained by all common genetic variants was 13%. Polygenic scores for the following traits and disorders were associated with SRH: cognitive ability, education, neuroticism, BMI, longevity, ADHD, major depressive disorder, schizophrenia, lung function, blood pressure, coronary artery disease, large vessel disease stroke, and type 2 diabetes. Conclusions Individual differences in how people respond to a single item on SRH are partly explained by their genetic propensity to many common psychiatric and physical disorders and psychological traits.

scholarly journals Educational Attainment Polygenic Scores, Socioeconomic Factors, and Cortical Structure in Children and Adolescents

2021 ◽  
Author(s):  
Emily C Merz ◽  
Jordan Strack ◽  
Hailee Hurtado ◽  
Uku Vainik ◽  
Michael Thomas ◽  
...  
Keyword(s):  
Academic Achievement ◽  
Educational Attainment ◽  
Socioeconomic Factors ◽  
Children And Adolescents ◽  
Parental Education ◽  
Genome Wide Association Study ◽  
Inferior Frontal Gyrus ◽  
Parahippocampal Gyrus ◽  
Genome Wide ◽  
Polygenic Scores

Background: Genome-wide polygenic scores for educational attainment (PGS-EA) and socioeconomic factors, which are correlated with each other, have been consistently associated with academic achievement and general cognitive ability in children and adolescents. Yet, the independent associations of PGS-EA and socioeconomic factors with specific underlying factors at the neural and neurocognitive levels are not well understood. The goal of this study was to examine the unique contributions of PGS-EA and parental education to cortical thickness (CT), cortical surface area (SA), and neurocognitive skills in children and adolescents. Methods: Participants were typically developing children and adolescents (3-21 years of age; 53% male; N = 391). High-resolution, T1-weighted magnetic resonance imaging data were acquired. PGS-EA were computed based on the most recent genome-wide association study of educational attainment. Sustained attention, inhibitory control, working memory, vocabulary, and episodic memory were measured. Results: PGS-EA and parental education were independently and significantly associated with SA, vocabulary, and attention outcomes but were not associated with CT. Vertex-wise analyses indicated that higher PGS-EA was significantly associated with greater SA in the left medial orbitofrontal gyrus and inferior frontal gyrus after accounting for parental education. Higher parental education was significantly associated with greater SA in the left parahippocampal gyrus after accounting for PGS-EA. Conclusions: These findings suggest that education-linked genetics may influence SA, particularly in certain frontal regions, leading to variability in academic achievement. Results suggested genetic confounding in associations between parental education and SA in children and adolescents, with these associations remaining significant after controlling for PGS-EA.

Sign in / Sign up

Export Citation Format

Share Document