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This study examines the temporal and geographical evolution of polygenic scores (PGSs) across cognitive measures (Educational Attainment [EA], Intelligence Quotient [IQ]), Socioeconomic Status (SES), and psychiatric conditions (Autism Spectrum Disorder [ASD], schizophrenia [SCZ]) in various populations. Our findings indicate positive directional selection for EA, IQ, and SES traits over the past 12,000 years. Schizophrenia and autism, while similar, showed different temporal patterns, aligning with theories suggesting they are psychological opposites. We observed a decline in PGS for neuroticism and depression, likely due to their genetic correlations and pleiotropic effects on intelligence. Significant PGS shifts from the Upper Paleolithic to the Neolithic periods suggest lifestyle and cognitive demand changes, particularly during the Neolithic Revolution. The study supports a mild hypothesis of Gregory Clark's model, showing a noticeable rise in genetic propensities for intelligence, academic achievement and professional status across Europe from the Middle Ages to the present. While latitude strongly influenced height, its impact on schizophrenia and autism was smaller and varied. Contrary to the cold winters theory, the study found no significant correlation between latitude and intelligence. [ABSTRACT FROM AUTHOR]

Background: While maternal at-risk drinking is associated with children's emotional and behavioral problems, there is a paucity of research that properly accounts for genetic confounding and gene–environment interplay. Therefore, it remains uncertain what mechanisms underlie these associations. We assess the moderation of associations between maternal at-risk drinking and childhood emotional and behavioral problems by common genetic variants linked to environmental sensitivity (genotype-by-environment [G × E] interaction) while accounting for shared genetic risk between mothers and offspring (GE correlation). Methods: We use data from 109 727 children born to 90 873 mothers enrolled in the Norwegian Mother, Father, and Child Cohort Study. Women self-reported alcohol consumption and reported emotional and behavioral problems when children were 1.5/3/5 years old. We included child polygenic scores (PGSs) for traits linked to environmental sensitivity as moderators. Results: Associations between maternal drinking and child emotional (β 1 = 0.04 [95% confidence interval (CI) 0.03–0.05]) and behavioral (β 1 = 0.07 [0.06–0.08]) outcomes attenuated after controlling for measured confounders and were almost zero when we accounted for unmeasured confounding (emotional: β 1 = 0.01 [0.00–0.02]; behavioral: β 1 = 0.01 [0.00–0.02]). We observed no moderation of these adjusted exposure effects by any of the PGS. Conclusions: The lack of strong evidence for G × E interaction may indicate that the mechanism is not implicated in this kind of intergenerational association. It may also reflect insufficient power or the relatively benign nature of the exposure in this sample. [ABSTRACT FROM AUTHOR]

Refugee children are often exposed to substantial trauma, placing them at increased risk for mental illness. However, this risk can be mitigated by a capacity for resilience, conferred from multiple ecological systems (e.g., family, community), including at an individual biological level. We examined the ability of hair cortisol concentrations and polygenic scores for mental health to predict risk and resilience in a sample of Syrian refugee children (n = 1359). Children were categorized as either at-risk or resilient depending on clinical thresholds for posttraumatic stress disorder, depression, and externalizing behavior problems. Logistic regression was used to examine main and interacting effects while controlling for covariates. Elevated hair cortisol concentrations were significantly associated with reduced resilience (odds ratio (OR)=0.58, 95%CI [0.40, 0.83]) while controlling for levels of war exposure. Polygenic scores for depression, self-harm, and neuroticism were not found to have any significant main effects. However, a significant interaction emerged between hair cortisol and polygenic scores for depression (OR=0.04, 95%CI [0.003 0.47]), suggesting that children predisposed to depression were more at risk for mental health problems when hair cortisol concentrations were high. Our results suggest that biomarkers (separately and in combination) might support early identification of refugee children at risk for mental health problems. [ABSTRACT FROM AUTHOR]

Abstract Background The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question. Aim To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample. Methods The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components. Results FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ. Conclusions PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients’ lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Background: Psychotic experiences and negative symptoms (PENS) are common in non-clinical populations. PENS are associated with adverse outcomes, particularly when they persist. Little is known about the trajectories of PENS dimensions in young people, nor about the precursory factors associated with these trajectories. Methods: We conducted growth mixture modelling of paranoia, hallucinations, and negative symptoms across ages 16, 17, and 22 in a community sample (N = 12 049–12 652). We then described the emergent trajectory classes through their associations with genome-wide polygenic scores (GPS) for psychiatric and educational phenotypes, and earlier childhood characteristics. Results: Three trajectory classes emerged for paranoia, two for hallucinations, and two for negative symptoms. Across PENS, GPS for clinical help-seeking, major depressive disorder, and attention deficit hyperactivity disorder were associated with increased odds of being in the most elevated trajectory class (OR 1.07–1.23). Lower education GPS was associated with the most elevated trajectory class for hallucinations and negative symptoms (OR 0.77–0.91). Conversely for paranoia, higher education GPS was associated with the most elevated trajectory class (OR 1.25). Trajectory class associations were not significant for schizophrenia, obsessive-compulsive disorder, bipolar disorder, or anorexia GPS. Emotional/behaviour problems and life events in childhood were associated with increased odds of being in the most elevated trajectory class across PENS. Conclusions: Our results suggest latent heterogeneity in the development of paranoia, hallucinations, and negative symptoms in young people that is associated with specific polygenic scores and childhood characteristics. [ABSTRACT FROM AUTHOR]

Background: Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. Methods: Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212–5369 per phenotype). Results: The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [ β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. Conclusions: Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene−environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults. Methods: Data were drawn from the English longitudinal study of ageing (N ~3400). Retrospective information on ACEs was collected in wave3 (2006/07). We calculated a cumulative risk score of ACEs and also assessed distinct dimensions separately. Depressive symptoms were ascertained on eight occasions, from wave1 (2002/03) to wave8 (2016/17). CRP was measured in wave2 (2004/05), wave4 (2008/09), and wave6 (2012/13). The associations of the risk factors with group-based depressive-symptom trajectories and repeated exposure to high CRP (i.e. ⩾3 mg/L) were tested using multinomial and ordinal logistic regression. Results: All types of ACEs were independently associated with high depressive-symptom trajectories (OR 1.44, 95% CI 1.30–1.60) and inflammation (OR 1.08, 95% CI 1.07–1.09). The risk of high depressive-symptom trajectories (OR 1.47, 95% CI 1.28–1.70) and inflammation (OR 1.03, 95% CI 1.01–1.04) was also higher for participants with higher MDD-PGS. G×E analyses revealed that the associations between ACEs and depressive symptoms were larger among participants with higher MDD-PGS (OR 1.13, 95% CI 1.04–1.23). ACEs were also more strongly related to inflammation in participants with higher CRP-PGS (OR 1.02, 95% CI 1.01–1.03). Conclusions: ACEs and polygenic susceptibility were independently and interactively associated with elevated depressive symptoms and chronic inflammation, highlighting the clinical importance of assessing both ACEs and genetic risk factors to design more targeted interventions. [ABSTRACT FROM AUTHOR]

This study focused on generality versus specificity of susceptibility of effects of eight family and child-care exposures measured between 3 and 54 months of age (e.g., sensitive parenting, child-care quality) on five child development outcomes assessed at age 4.5 years (e.g. behavior problems, preacademic skill), using data from The National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (n = 1,364, boys = 705; White = 1,097, Black = 176, other = 91), while applying a novel influence-statistics method. Results indicated that susceptibility across the environment-predictor:child-outcome associations is normally rather than bimodally (i.e., orchid–dandelion) distributed. Analysis of susceptibility documents both domain generality and specificity of developmental plasticity, with effect sizes proving small in the former case. As predicted, children who as infants had difficult temperaments or who scored higher on a polygenic-plasticity score (serotonin-transporter-linked promoter region [ 5-HTTLPR ], dopamine receptor D4 [ DRD4 ], brain-derived neurotrophic factor [ BDNF ]) proved somewhat more susceptible to some of the environmental effects investigated. Results lead to the recommendation that two-types-of-individuals vis-a-vis susceptibility to environmental influences be questioned and general-trait conceptions of susceptibility be further investigated. [ABSTRACT FROM AUTHOR]

The sociogenomics revolution is upon us, we are told. Whether revolutionary or not, sociogenomics is poised to flourish given the ease of incorporating polygenic scores (or PGSs) as "genetic propensities" for complex traits into social science research. Pointing to evidence of ubiquitous heritability and the accessibility of genetic data, scholars have argued that social scientists not only have an opportunity but a duty to add PGSs to social science research. Social science research that ignores genetics is, some proponents argue, at best partial and likely scientifically flawed, misleading, and wasteful. Here, I challenge arguments about the value of genetics for social science and with it the claimed necessity of incorporating PGSs into social science models as measures of genetic influences. In so doing, I discuss the impracticability of distinguishing genetic influences from environmental influences because of non-causal gene–environment correlations, especially population stratification, familial confounding, and downward causation. I explain how environmental effects masquerade as genetic influences in PGSs, which undermines their raison d'être as measures of genetic propensity, especially for complex socially contingent behaviors that are the subject of sociogenomics. Additionally, I draw attention to the partial, unknown biology, while highlighting the persistence of an implicit, unavoidable reductionist genes versus environments approach. Leaving sociopolitical and ethical concerns aside, I argue that the potential scientific rewards of adding PGSs to social science are few and greatly overstated and the scientific costs, which include obscuring structural disadvantages and cultural influences, outweigh these meager benefits for most social science applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The DNA revolution has energized research on interactions between genes and environments (GxE) by creating indices of G (polygenic scores) that are powerful predictors of behavioral traits. Here, we test the extent to which polygenic scores for attention-deficit/hyperactivity disorder and neuroticism moderate associations between parent reports of their children's environmental risk (E) at ages 3 and 4 and teacher ratings of behavior problems (hyperactivity/inattention, conduct problems, emotional symptoms, and peer relationship problems) at ages 7, 9 and 12. The sampling frame included up to 6687 twins from the Twins Early Development Study. Our analyses focused on relative effect sizes of G, E and GxE in predicting behavior problems. G, E and GxE predicted up to 2%, 2% and 0.4%, respectively, of the variance in externalizing behavior problems (hyperactivity/inattention and conduct problems) across ages 7, 9 and 12, with no clear developmental trends. G and E predictions of emotional symptoms and peer relationship problems were weaker. A quarter (12 of 48) of our tests of GxE were nominally significant (p =.05). Increasing the predictive power of G and E would enhance the search for GxE. [ABSTRACT FROM AUTHOR]

Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age2, cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene-environment correlation with adolescent alcohol use at all PGS thresholds (ps <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (ΔR2 ranged from 0.5% to 1.1%). The positive gene-environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors. [ABSTRACT FROM AUTHOR]

Background: Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a 'genome-wide association study (GWAS) by subtraction,' subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal 'cognitive' and 'non-cognitive' factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear., Methods: Using data from up to 5517 youth (ages 9-11) of European ancestry from the ongoing Adolescent Brain Cognitive Development SM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects., Results: Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects., Conclusions: While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.

Background: Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations., Methods: This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples., Results: We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18-0.34, p = 8.5 × 10 -6 ). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI -0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06-0.08), female sex (beta = 0.160, 95% CI 0.15-0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03-0.07), while neither the depression PGS (beta = 0.004, 95% CI -0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI -0.01 to 0.03) were strongly associated with MDD., Conclusions: Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Background. Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs). Methods. PRSs from The Danish High-Risk and Resilience Study—VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115). Results. The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation. Conclusions. Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract Background Psychiatric disorders are highly polygenic and show patterns of partner resemblance. Partner resemblance has direct population-level genetic implications if it is caused by assortative mating, but not if it is caused by convergence or social homogamy. Using genetics may help distinguish these different mechanisms. Here, we investigated whether partner resemblance for schizophrenia and bipolar disorder is influenced by assortative mating using polygenic risk scores (PRSs). Methods PRSs from The Danish High-Risk and Resilience Study—VIA 7 were compared between parents in three subsamples: population-based control parent pairs (N=198), parent pairs where at least one parent had schizophrenia (N=193), and parent pairs where at least one parent had bipolar disorder (N=115). Results The PRS for schizophrenia was predictive of schizophrenia in the full sample and showed a significant correlation between parent pairs (r=0.121, p=0.0440), indicative of assortative mating. The PRS for bipolar disorder was also correlated between parent pairs (r=0.162, p=0.0067), but it was not predictive of bipolar disorder in the full sample, limiting the interpretation. Conclusions Our study provides genetic evidence for assortative mating for schizophrenia, with important implications for our understanding of the genetics of schizophrenia.

Background: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk., Methods: Data came from the Collaborative Study on the Genetics of Alcoholism ( n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones., Results: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20)., Conclusions: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Using data from the Midlife Development in the USA (MIDUS) sample (3070 men and 3182 women) and the Wisconsin Longitudinal Study (WLS; 2240 men and 2346 women), we aimed to investigate whether religious, ethnic and racial in-group preferences as well as religious homogamy are associated with reproductive outcome in terms of number of children. Using data from the MIDUS twin sample, we further estimated the inherited genetic component of in-group attitudes. Additionally, we analyzed the association of ∼50 polygenic scores (PGSs) recently published for the WLS study and in-group attitudes as an indicator of potential pleiotropic effects. We found in both samples that, with one exception, religious though not other in-group attitudes are associated with a higher reproductive outcome. Also, religious homogamy is associated with higher average number of children. The inherited component of all in-group attitudes ranges from ∼21% to 45% (MIDUS twin sample). PGSs associated with religious behavior are significantly positively associated with religious in-group attitudes as well as family attitudes. Further associations are found with PGS on life satisfaction (work) and, negatively, with PGS for any sort of addiction (smoking, alcohol and cannabis use), indicating pleiotropy. We conclude that the positive association between religious in-group attitudes as well as religious homogamy and reproductive outcome may indicate selective forces on religious in-group behavior. As all investigated in-group attitudes, however, have a substantial inherited component, we further speculate that potential previous reproductive benefits of racial and ethnic in-group preferences, if they ever existed, might have been substituted by religious in-group preferences. [ABSTRACT FROM AUTHOR]

Background: Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. Methods: Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). Results: ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. Conclusion: Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question., Aim: To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample., Methods: The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components., Results: FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ., Conclusions: PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients' lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Using newly available polygenic scores for educational attainment and cognitive ability, this paper investigates the possible presence and causes of a negative association between IQ and fertility in the Wisconsin Longitudinal Study sample, an issue that Retherford and Sewell first addressed 30 years ago. The effect of the polygenic score on the sample's reproductive characteristics was indirect: a latent cognitive ability measure, comprised of both educational attainment and IQ, wholly mediated the relationship. Age at first birth mediated the negative effect of cognitive ability on sample fertility, which had a direct (positive) effect on the number of grandchildren. Significantly greater impacts of cognitive ability on the sample's fertility characteristics were found among the female subsample. This indicates that, in this sample, having a genetic disposition toward higher cognitive ability does not directly reduce number of offspring; instead, higher cognitive ability is a risk factor for prolonging reproductive debut, which, especially for women, reduces the fertility window and, thus, the number of children and grandchildren that can be produced. By estimating the effect of the sample's reproductive characteristics on the strength of polygenic selection, it was found that the genetic variance component of IQ should be declining at a rate between -.208 (95% CI [-.020, -.383]) and -.424 (95% CI [-.041, -.766]) points per decade, depending on whether GCTA-GREML or classical behavior genetic estimates of IQ heritability are used to correct for 'missing' heritability. [ABSTRACT FROM AUTHOR]

Alcohol use is influenced by genetic and environmental factors. We examined the interactive effects between genome-wide polygenic risk scores for alcohol use (alc-PRS) and social support in relation to alcohol use among European American (EA) and African American (AA) adults across sex and developmental stages (emerging adulthood, young adulthood, and middle adulthood). Data were drawn from 4,011 EA and 1,274 AA adults from the Collaborative Study on the Genetics of Alcoholism who were between ages 18-65 and had ever used alcohol. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism and provided saliva or blood samples for genotyping. Results indicated that social support from friends, but not family, moderated the association between alc-PRS and alcohol use among EAs and AAs (only in middle adulthood for AAs); alc-PRS was associated with higher levels of alcohol use when friend support was low, but not when friend support was high. Associations were similar across sex but differed across developmental stages. Findings support the important role of social support from friends in buffering genetic risk for alcohol use among EA and AA adults and highlight the need to consider developmental changes in the role of social support in relation to alcohol use.

Human populations living during the Holocene underwent considerable microevolutionary change. It has been theorized that the transition of Holocene populations into agrarianism and urbanization brought about culture-gene co-evolution that favored via directional selection genetic variants associated with higher general cognitive ability (GCA). To examine whether GCA might have risen during the Holocene, we compare a sample of 99 ancient Eurasian genomes (ranging from 4.56 to 1.21 kyr BP) with a sample of 503 modern European genomes (Fst = 0.013), using three different cognitive polygenic scores (130 SNP, 9 SNP and 11 SNP). Significant differences favoring the modern genomes were found for all three polygenic scores (odds ratios = 0.92, p = 001; .81, p = 037; and .81, p = .02 respectively). These polygenic scores also outperformed the majority of scores assembled from random SNPs generated via a Monte Carlo model (between 76.4% and 84.6%). Furthermore, an indication of increasing positive allele count over 3.25 kyr was found using a subsample of 66 ancient genomes (r = 0.22, pone-tailed = .04). These observations are consistent with the expectation that GCA rose during the Holocene. [ABSTRACT FROM AUTHOR]

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.