scholarly journals The Positive End of the Polygenic Score Distribution for ADHD: A Low Risk or a Protective Factor?

2019 ◽  
Author(s):  
James J. Li
Keyword(s):  
Educational Attainment ◽  
Functional Outcomes ◽  
Protective Factor ◽  
Genome Wide Association Study ◽  
Add Health ◽  
Later Life ◽  
Low Risk ◽  
Score Distribution ◽  
Genetic Liability ◽  
Polygenic Scores

AbstractBackgroundPolygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood.MethodsParticipants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N=7,088; mean age=29, s.d.=1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health and physical health were assessed during in-home interviews.ResultsIndividuals at the lowest end of the ADHD PGS distribution (i.e., lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17-19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high PGS groups.ConclusionsFindings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.

scholarly journals The positive end of the polygenic score distribution for ADHD: a low risk or a protective factor?

2019 ◽  
pp. 1-10 ◽  
Author(s):  
James J. Li
Keyword(s):  
Educational Attainment ◽  
Functional Outcomes ◽  
Protective Factor ◽  
Genome Wide Association Study ◽  
Add Health ◽  
Later Life ◽  
Low Risk ◽  
Score Distribution ◽  
Genetic Liability ◽  
Polygenic Scores

Abstract Background Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood. Methods Participants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N = 7088; mean age = 29, s.d. = 1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health, and physical health were assessed during in-home interviews. Results Individuals at the lowest end of the ADHD PGS distribution (i.e. lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17–19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high-PGS groups. Conclusions Findings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.

scholarly journals Common health conditions in childhood and adolescence, school absence, and educational attainment: Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Amanda Hughes ◽  
Kaitlin H. Wade ◽  
Matt Dickson ◽  
Frances Rice ◽  
Alisha Davies ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Educational Outcomes ◽  
Good Health ◽  
Negative Influence ◽  
Autism Spectrum ◽  
Health Conditions ◽  
Childhood And Adolescence ◽  
Genetic Liability ◽  
School Absence ◽  
Polygenic Scores

AbstractGood health is positively related to children’s educational outcomes, but relationships may not be causal. Demonstrating a causal influence would strongly support childhood and adolescent health as important for education policy. We applied genetic causal inference methods to assess the causal relationship of common health conditions at age 10 (primary/elementary school) and 13 (mid-secondary/mid-high school) with educational attainment at 16 and school absence at 14–16. Participants were 6113 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Exposures were symptoms of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, asthma, migraines and BMI. Genetic liability for these conditions and BMI was indexed by polygenic scores. In non-genetic, multivariate-adjusted models, all health conditions except asthma and migraines were associated with poorer attainment and greater school absence. School absence substantially mediated effects of BMI (39.9% for BMI at 13) and migraines (72.0% at 10), on attainment with more modest mediation for emotional and neurodevelopmental conditions. In genetic models, a unit increase in standardized BMI at 10 predicted a 0.19 S.D. decrease (95% CI: 0.11, 0.28) in attainment at 16, equivalent to around a 1/3 grade lower in all subjects, and 8.7% more school absence (95% CI:1.8%,16.1%). Associations were similar at 13. Genetic liability for ADHD predicted lower attainment but not more absence. Triangulation across multiple approaches supports a causal, negative influence on educational outcomes of BMI and ADHD, but not of ASD, depression, asthma or migraine. Higher BMI in childhood and adolescence may causally impair educational outcomes.

scholarly journals Identification of 370 loci for age at onset of sexual and reproductive behaviour, highlighting common aetiology with reproductive biology, externalizing behaviour and longevity

2020 ◽  
Author(s):  
Melinda C. Mills ◽  
Felix C. Tropf ◽  
David M. Brazel ◽  
Natalie van Zuydam ◽  
Ahmad Vaez ◽  
...  
Keyword(s):  
Reproductive Biology ◽  
Genome Wide Association Study ◽  
Age At Onset ◽  
Later Life ◽  
Reproductive Behaviour ◽  
Age At First Birth ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Externalizing Behaviour

AbstractThe timing of reproductive behaviour – age at first sexual intercourse (AFS) and age at first birth (AFB) – has implications for reproductive health, adolescent development and evolutionary fitness. In the largest genome-wide association study to date (AFS, N=387,338; AFB, N=542,901), we identify 370 independent signals, 11 which are sex-specific, with a 5-6% polygenic score prediction. Heritability shifted from 10% for those born in 1940 to 23% for the 1965 birth cohort. Using Genomic SEM, we show that signals are largely driven by the genetics of reproductive biology and externalizing behaviour. This is supported by extensive biological follow-up that isolates key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility (endometriosis, spontaneous abortion) and spermatid differentiation, morphogenesis and binding (KLF17, ZPBP). Later AFB is protective against later-life disease (type 2 diabetes, cardiovascular) and associated with longevity. Those from higher childhood socioeconomic circumstances and polygenic scores in the highest deciles (90%+) experience markedly later reproductive onset. Results are relevant for interventions in teenage sexual, reproductive and mental health, deepen our understanding of the drivers of later-life health and longevity, and fuel infertility and functional follow-up experiments.

scholarly journals Association of Leisure Activities With Cognitive Impairment and Dementia in Older Adults in Colombia: A SABE-Based Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Alejandra Guerrero Barragán ◽  
Diego Lucumí ◽  
Brian Lawlor
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Educational Attainment ◽  
Protective Factor ◽  
Leisure Activities ◽  
Later Life ◽  
Multinomial Regression ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
State Examination

Observational and interventional studies suggest that participation in leisure activities may help protect against cognitive decline in older people. This study aimed to examine the association between participation in leisure activities and cognitive impairment in older adults in Colombia. Data for this study were derived from the Colombian National Survey of Aging (SABE 2015), a cross-sectional survey with a sample size of 23,694 older adults representing the total population (mean age, 70.8 years; 57.3% females). Cognitive impairment was classified as cognitive impairment without dementia (CIWD) and dementia, according to the revised version of the Folstein Mini-Mental State Examination and the Lawton and Brody functional scale. Leisure activities were evaluated using six items of a questionnaire. Sex-stratified multinomial regression models were used to analyze the association of leisure activities with CIWD and dementia after adjusting for educational attainment, literacy, and other potential confounders. In adjusted models for men, leisure activities in later life were associated with a decreased risk of CIWD (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.68–0.78) and dementia (OR, 0,52; 95% CI, 0.48–0.58). For women, leisure activities in later life were associated with a decreased risk of CIWD (OR, 0.72; 95% CI, 0.66–0.78) and dementia (OR, 0.48; 95% CI, 0.43–0.53). The findings suggest that greater participation in leisure activities in later life may act as a protective factor against CIWD and dementia among older adults in Colombia, independent of educational attainment and literacy.

scholarly journals A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains

2018 ◽  
Vol 29 (8) ◽  
pp. 3496-3504 ◽  
Author(s):  
Maxwell L Elliott ◽  
Daniel W Belsky ◽  
Kevin Anderson ◽  
David L Corcoran ◽  
Tian Ge ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Test Performance ◽  
Genome Wide Association Study ◽  
Brain Size ◽  
Imaging Genetics ◽  
Cognitive Test ◽  
Total Brain Volume ◽  
A Genome ◽  
Polygenic Scores ◽  
Cognitive Test Performance

Abstract People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to the development of larger brains. We tested this hypothesis using four large imaging genetics studies (combined N = 7965) with polygenic scores derived from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We conducted meta-analysis to test associations among participants’ genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants’ education polygenic scores and their cognitive test performance. Effect sizes were larger in the population-based samples than in the convenience-based samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging to understand neurobiology linking genetics with cognitive performance.

scholarly journals Genetic liability to schizophrenia is associated with exposure to traumatic events in childhood

2020 ◽  
pp. 1-8 ◽  
Author(s):  
Hannah M. Sallis ◽  
Jazz Croft ◽  
Alexandra Havdahl ◽  
Hannah J. Jones ◽  
Erin C. Dunn ◽  
...  
Keyword(s):  
Childhood Trauma ◽  
Genome Wide Association Study ◽  
Trauma Exposure ◽  
Positive Association ◽  
Childhood And Adolescence ◽  
Birth Cohorts ◽  
Genetic Liability ◽  
Healthy Environment ◽  
Parents And Children ◽  
Polygenic Scores

Abstract Background There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene–environment correlation. Methods The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0–17 years; ALSPAC) and at age 8 years (MoBa). Results Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure. Conclusions Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment.

scholarly journals Genomic variation in educational attainment modifies Alzheimer disease risk

2019 ◽  
Vol 5 (2) ◽  
pp. e310 ◽  
Author(s):  
Neha S. Raghavan ◽  
Badri Vardarajan ◽  
Richard Mayeux
Keyword(s):  
Alzheimer Disease ◽  
Educational Attainment ◽  
Causal Relationship ◽  
Instrumental Variable ◽  
Protective Factor ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Genomic Variation ◽  
Genome Wide

ObjectiveTo determine the putative protective relationship of educational attainment on Alzheimer disease (AD) risk using Mendelian randomization and to test the hypothesis that by using genetic regions surrounding individually associated single nucleotide polymorphisms (SNPs) as the instrumental variable, we can identify genes that contribute to the relationship.MethodsWe performed Mendelian randomization using genome-wide association study summary statistics from studies of educational attainment and AD in two stages. Our instrumental variable comprised (1) 1,271 SNPs significantly associated with educational attainment and (2) individual 2-Mb regions surrounding the genome-wide significant SNPs.ResultsA causal inverse relationship between educational attainment and AD was identified by the 1,271 SNPs (odds ratio = 0.63; 95% confidence interval, 0.54–0.74; p = 4.08 x 10−8). Analysis of individual loci identified 2 regions that significantly replicated the causal relationship. Genes within these regions included LRRC2, SSBP2, and NEGR1; the latter a regulator of neuronal growth.ConclusionsEducational attainment is an important protective factor for AD. Genomic regions that significantly paralleled the overall causal relationship contain genes expressed in neurons or involved in the regulation of neuronal development.

scholarly journals Cleft lip/palate and educational attainment: cause, consequence or correlation? A Mendelian randomization study

2020 ◽  
Vol 49 (4) ◽  
pp. 1282-1293 ◽  
Author(s):  
Christina Dardani ◽  
Laurence J Howe ◽  
Nandita Mukhopadhyay ◽  
Evie Stergiakouli ◽  
Yvonne Wren ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Genetic Correlation ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Genetic Liability ◽  
Performance Factors ◽  
A Genome ◽  
Cleft Lip Palate

Abstract Background Previous studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment. Methods We performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence. Results There was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) −0.05, 95% confidence interval (CI) −0.12 to 0.01, P 0.13; MR estimate (βMR) −0.002, 95% CI −0.009 to 0.006, P 0.679) or intelligence (rg −0.04, 95% CI −0.13 to 0.04, P 0.34; βMR −0.009, 95% CI −0.02 to 0.002, P 0.11). Conclusions Common variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.

Social Integration, Self-Rated Health . . . and Genes?

2019 ◽  
Vol 32 (5-6) ◽  
pp. 462-471
Author(s):  
Aniruddha Das
Keyword(s):  
Educational Attainment ◽  
Social Integration ◽  
Capital Accumulation ◽  
Community Integration ◽  
Later Life ◽  
Two Dimensions ◽  
Genetic Associations ◽  
Self Rated Health ◽  
Polygenic Scores ◽  
Stakeholder Network

Objective: This study examined genetic roots of later life social integration, and their confounding of this social factor’s health linkages. Method: Data were from the 2010 wave of the Health and Retirement Study. Two dimensions of integration were examined: with one’s “stakeholder” network of family and friends and with the community. Genetic measures included polygenic scores for extraversion and educational attainment. Results: Ties to one’s stakeholder network had no genetic associations. The extraversion polygenic score was linked to community integration among Blacks as well as Whites. Among the latter, the same was true of one’s genetic propensity for educational attainment. Although this score also influenced self-rated health, neither confounded associations of social integration with this indicator. Discussion: Later life social integration seems influenced by genetically rooted propensities for both sociability and human capital accumulation. Health linkages of integration, however, may not reflect mutual dependencies on the same genetic substrates.

scholarly journals The Effects of Education on Cognition in Older Age: Evidence from Genotyped Siblings

2021 ◽  
Author(s):  
Jason Fletcher ◽  
Michael Topping ◽  
Fengyi Zheng ◽  
Qiongshi Lu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Educational Attainment ◽  
College Graduates ◽  
Family Background ◽  
Later Life ◽  
Older Age ◽  
The United Kingdom ◽  
Genetic Predictors ◽  
Polygenic Scores

A growing literature has sought to tie educational attainment with later-life cognition and Alzheimer's disease outcomes. This paper leverages sibling comparisons in educational attainment as well as genetic predictors (polygenic scores) for cognition, educational attainment, and Alzheimer's disease to estimate effects of educational attainment on cognition in older age in the United Kingdom. We find that the effects of education on cognition are confounded by family background factors (~40%) and by genetics (<10%). After adjustments, we continue to find large effects of education. College graduates have cognition scores that are approximately 0.75 SD higher than those who report no credentials. We also find evidence that educational effects on cognition are smaller for those with high polygenic scores for Alzheimer's disease.

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