Associations between depression and cardiometabolic health: A 27-year longitudinal study

Abstract Background Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems. Methods The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)]. Results Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60). Conclusions A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

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A prospective study of artificially sweetened beverage intake and cardiometabolic health among women at high risk

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz094 ◽

2019 ◽

Vol 110 (1) ◽

pp. 221-232 ◽

Cited By ~ 7

Author(s):

Stefanie N Hinkle ◽

Shristi Rawal ◽

Anne Ahrendt Bjerregaard ◽

Thor I Halldorsson ◽

Mengying Li ◽

...

Keyword(s):

High Risk ◽

Liver Fat ◽

Sensitivity Analyses ◽

Cardiometabolic Health ◽

Cross Sectional ◽

Reverse Causation ◽

Clinical Exam ◽

Prepregnancy Bmi ◽

In Pregnancy

ABSTRACT Background Artificially sweetened beverages (ASBs) are commonly consumed and recommended for individuals at high risk for cardiometabolic diseases; however, the health effects of ASBs remain contradictory. Given that cross-sectional analyses are subject to reverse causation, prospective studies with long-term follow-up are needed to evaluate associations between ASBs and cardiometabolic health, especially among high-risk individuals. Objective The aim of this study was to examine associations of ASB intake and cardiometabolic health among high-risk women with prior gestational diabetes mellitus (GDM). Methods We included 607 women with GDM from the Danish National Birth Cohort (DNBC; 1996–2002) who completed a clinical exam 9–16 y after the DNBC pregnancy for the Diabetes & Women's Health (DWH) Study (2012–2014). We assessed ASB intake using FFQs completed during the DNBC pregnancy and at the DWH Study clinical exam. We examined cardiometabolic outcomes at the DWH clinical exam. We estimated percentage differences in continuous cardiometabolic markers and RRs for clinical endpoints in association with ASB intake both during pregnancy and at follow-up adjusted for prepregnancy BMI, diet, and lifestyle factors. Sensitivity analyses to account for reverse causation were performed. Results In pregnancy and at follow-up, 30.4% and 36.4% of women regularly (≥2 servings/wk) consumed ASB, respectively. Consumption of ASBs, both during pregnancy and at follow-up, was associated with higher glycated hemoglobin (HbA1c), insulin, HOMA-IR, triglycerides, liver fat, and adiposity and with lower HDL at follow-up. After adjustment for covariates, particularly prepregnancy BMI, the majority of associations between ASB intake in pregnancy and outcomes at follow-up became null with the exception of HbA1c. ASB intake at follow-up (≥1 serving/d compared with <1 serving/mo) was associated with higher HbA1c (6.5%; 95% CI: 1.9, 11.3; P-trend = 0.007); however, associations were not upheld in sensitivity analyses for reverse causation. Conclusions Among Danish women with a history of GDM, ASB intake was not significantly associated with cardiometabolic profiles.

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Polygenic Risk for Major Depression Interacts with Parental Criticism in Predicting Adolescent Depressive Symptom Development

Journal of Youth and Adolescence ◽

10.1007/s10964-020-01353-4 ◽

2020 ◽

Author(s):

Stefanie A. Nelemans ◽

Marco Boks ◽

Bochao Lin ◽

Tineke Oldehinkel ◽

Pol van Lier ◽

...

Keyword(s):

Depressive Symptoms ◽

Depressive Symptom ◽

Major Depression ◽

Meta Analysis ◽

Late Adolescence ◽

Sensitivity Analyses ◽

Polygenic Risk Score ◽

Environment Interaction ◽

Symptom Development ◽

Polygenic Risk

AbstractResearch has focused more and more on the interplay between genetics and environment in predicting different forms of psychopathology, including depressive symptoms. While the polygenic nature of depressive symptoms is increasingly recognized, only few studies have applied a polygenic approach in gene-by-environment interaction (G × E) studies. Furthermore, longitudinal G × E studies on developmental psychopathological properties of depression are scarce. Therefore, this 6-year longitudinal community study examined the interaction between genetic risk for major depression and a multi-informant longitudinal index of critical parenting in relation to depressive symptom development from early to late adolescence. The sample consisted of 327 Dutch adolescents of European descent (56% boys; Mage T1 = 13.00, SDage T1 = 0.44). Polygenic risk for major depression was based on the Hyde et al. (Nature Genetics, 48, 1031–1036, 2016) meta-analysis and genetic sensitivity analyses were based on the 23andMe discovery dataset. Latent Growth Models suggested that polygenic risk score for major depression was associated with higher depressive symptoms across adolescence (significant main effect), particularly for those experiencing elevated levels of critical parenting (significant G × E). These findings highlight how polygenic risk for major depression in combination with a general environmental factor impacts depressive symptom development from early to late adolescence.

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Prenatal smoking, alcohol and caffeine exposure and ADHD risk in childhood: parental comparisons and polygenic risk score (PRS) analyses

10.1101/2021.03.25.21254087 ◽

2021 ◽

Author(s):

Elis Haan ◽

Hannah M Sallis ◽

Luisa Zuccolo ◽

Jeremy Labrecque ◽

Eivind Ystrom ◽

...

Keyword(s):

Substance Use ◽

Coffee Consumption ◽

Negative Control ◽

Sensitivity Analyses ◽

Risk Scores ◽

Prenatal Smoking ◽

Polygenic Risk Score ◽

Caffeine Consumption ◽

Polygenic Risk ◽

Prenatal Substance Use

Background and aims: Several studies have indicated that maternal prenatal substance use may be associated with offspring ADHD via intrauterine effects. We investigated associations between maternal prenatal smoking, alcohol and caffeine consumption with childhood ADHD risk accounting for shared familial factors. Design: First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders); adjusted (including confounders) and mutually adjusted (including confounders and partners substance use). The results were meta-analysed across the cohorts. Second, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for genetic variants of smoking, alcohol and coffee consumption were regressed against ADHD risk. We triangulated the results across the two approaches to infer causality. Setting: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants: Phenotype data available for children was: N(ALSPAC)=7,850; N(GENR)=3,849 and N(MOBA)=43,512. Genotype data available for mothers was: N(ALSPAC)=7,074 and N(MOBA)=14,583. Measurements: Offspring ADHD risk around age 7-8 was derived by dichotomising symptom scores from multiple questionnaires and parental self-reported substance use was measured at the 2nd pregnancy trimester. Findings: The pooled estimate for maternal prenatal substance use showed an association with ADHD risk (OR_SMOKING=1.11, 95%CI 1.00-1.23; OR_ALCOHOL=1.27, 95%CI 1.08-1.49; OR_CAFFEINE=1.05, 95%CI 1.00-1.11), while not for fathers (OR_SMOKING=1.03, 95%CI 0.95-1.13; OR_ALCOHOL=0.83, 95%CI 0.47-1.48; OR_CAFFEINE=1.02, 95%CI 0.97-1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD in MoBa). The PRS analyses did not show evidence of association in ALSPAC or MoBa. Conclusions: Our results do not provide support for a causal intrauterine effect of maternal prenatal substance use on offspring attention-deficit hyperactivity disorder risk.

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Anxiety, Depression, and Colorectal Cancer Survival: Results from Two Prospective Cohorts

Journal of Clinical Medicine ◽

10.3390/jcm9103174 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3174

Author(s):

Claudia Trudel-Fitzgerald ◽

Shelley S. Tworoger ◽

Xuehong Zhang ◽

Edward L. Giovannucci ◽

Jeffrey A. Meyerhardt ◽

...

Keyword(s):

Colorectal Cancer ◽

Fixed Effects ◽

Cox Regression ◽

Sensitivity Analyses ◽

Disease Stage ◽

Health Study ◽

Anxiety And Depression ◽

Depression Symptoms ◽

Standard Deviation Increase

Given the unalterable nature of most risk factors for colorectal cancer (CRC) survival (e.g., disease stage), identifying modifiable determinants is critical. We investigated whether anxiety and depression were related to CRC survival using data from the Nurses’ Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants who received a CRC diagnosis and provided information about anxiety (nNHS = 335; nHPFS = 232) and depression (nNHS = 893; nHPFS = 272) within 4 years of diagnosis were included. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) of overall mortality, while controlling for covariates (sociodemographics, cancer characteristics, and lifestyle factors). Pooled risk estimates were derived from fixed effects meta-analyses of the cohorts. Among 1732 CRC patients, 814 deaths occurred during the 28-year follow-up. Each 1 standard deviation increase in anxiety or depression symptoms was associated with a similar 16% higher mortality risk (anxiety: 95% CI = 1.05–1.29; depression: 95% CI = 1.07–1.26). Comparable results were observed across all sensitivity analyses (introducing a 1-year lag, restricting to CRC-related mortality, considering potential behavioral pathways) and stratified models (cancer stage, sex). Our findings suggest greater anxiety and depression symptoms can not only impede adherence to healthy habits and reduce quality of life in cancer patients but could also be a marker for accelerated CRC progression.

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Evaluating the prognostic performance of a polygenic risk score for breast cancer risk stratification

BMC Cancer ◽

10.1186/s12885-021-08937-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maria Olsen ◽

Krista Fischer ◽

Patrick M. Bossuyt ◽

Els Goetghebeur

Keyword(s):

Breast Cancer ◽

Cancer Incidence ◽

Cox Regression ◽

Breast Cancer Incidence ◽

Independent Study ◽

Risk Scores ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Prognostic Performance

Abstract Background Polygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. Before a PRS can be considered for implementation, it needs rigorous evaluation, using performance measures that can inform about its future clinical value. Objectives To evaluate the prognostic performance of a regression model with a previously developed, prevalence-based PRS and age as predictors for breast cancer incidence in women from the Estonian biobank (EstBB) cohort; to compare it to the performance of a model including age only. Methods We analyzed data on 30,312 women from the EstBB cohort. They entered the cohort between 2002 and 2011, were between 20 and 89 years, without a history of breast cancer, and with full 5-year follow-up by 2015. We examined PRS and other potential risk factors as possible predictors in Cox regression models for breast cancer incidence. With 10-fold cross-validation we estimated 3- and 5-year breast cancer incidence predicted by age alone and by PRS plus age, fitting models on 90% of the data. Calibration, discrimination, and reclassification were calculated on the left-out folds to express prognostic performance. Results A total of 101 (3.33‰) and 185 (6.1‰) incident breast cancers were observed within 3 and 5 years, respectively. For women in a defined screening age of 50–62 years, the ratio of observed vs PRS-age modelled 3-year incidence was 0.86 for women in the 75–85% PRS-group, 1.34 for the 85–95% PRS-group, and 1.41 for the top 5% PRS-group. For 5-year incidence, this was respectively 0.94, 1.15, and 1.08. Yet the number of breast cancer events was relatively low in each PRS-subgroup. For all women, the model’s AUC was 0.720 (95% CI: 0.675–0.765) for 3-year and 0.704 (95% CI: 0.670–0.737) for 5-year follow-up, respectively, just 0.022 and 0.023 higher than for the model with age alone. Using a 1% risk prediction threshold, the 3-year NRI for the PRS-age model was 0.09, and 0.05 for 5 years. Conclusion The model including PRS had modest incremental performance over one based on age only. A larger, independent study is needed to assess whether and how the PRS can meaningfully contribute to age, for developing more efficient screening strategies.

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Ejaculation frequency and prostate cancer: A large, prospective study with 16 years of follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5078 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5078-5078

Author(s):

Jennifer R Rider ◽

Kathryn M Wilson ◽

Philip W. Kantoff ◽

Edward L. Giovannucci ◽

Lorelei A. Mucci

Keyword(s):

Prostate Cancer ◽

Erectile Dysfunction ◽

Prospective Study ◽

Average Frequency ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Average Lifetime ◽

High Grade ◽

Ejaculation Frequency

5078 Background: A prospective study in the Health Professionals Follow-up Study (HPFS) cohort published in 2001 found significantly lower risks of prostate cancer (PCa) among men with more frequent ejaculation. Because associations were stronger among men at older ages, which could be indicative of reverse causation (i.e., men ejaculating less because of symptoms associated with PCa) and few advanced cases were included, we conducted an updated study with an additional 8 years of follow up. Methods: We included 31,929 men aged 46-81 years from the HPFS who answered ejaculation frequency questions on the 1992 questionnaire. We assessed average frequency per month at three time points: age 20-29, age 40-49, and in 1991 (the year prior to the questionnaire). These data were also combined to estimate average lifetime frequency. Using follow up through January 31, 2008, we used Cox proportional hazards models to estimate relative risks (RR) and 95% confidence intervals (95% CI) for total PCa risk, as well as risk of advanced, lethal, and high-grade (Gleason 8-10) disease. As sensitivity analyses, we also examined associations within a subgroup of highly screened men and a subgroup of men without erectile dysfunction at baseline. Results: During 16 years of follow up, 3403 men were diagnosed with PCa; 455 were advanced, 360 were high grade, and 304 were lethal. Three percent of men reported a lifetime average frequency of >21 times per month while 34% reported 4-7 times per month. Compared to a frequency of 4-7 times per month, multivariate RRs for total PCa for men with >21 ejaculations per month were 0.81 (95% CI: 0.71-0.91) for ages 20-29; 0.76 (95% CI: 0.66-0.88) for ages 40-49; 0.68 (95% CI: 0.53-0.86) in 1991; and 0.57 (95% CI: 0.43-0.75) for lifetime average frequency. RRs for advanced PCa were of similar magnitudes at ages 20-29 years and 40-49 years but not statistically significant. Results were similar when we included only highly screened men or men without a history of erectile dysfunction. Conclusions: With extended follow up, ejaculation frequency continues to be strongly inversely associated with risk of total PCa. These findings are unlikely to be attributable to underlying disease or screening frequency.

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F92. Polygenic Risk Score from Schizophrenia Predicts PTSD and Depression Symptoms After Trauma Exposure

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.629 ◽

2019 ◽

Vol 85 (10) ◽

pp. S248

Author(s):

Adriana Lori ◽

Vasiliki Michopoulos ◽

Sterling Winters ◽

Kimberly Kerley ◽

Guia Guffanti ◽

...

Keyword(s):

Risk Score ◽

Trauma Exposure ◽

Depression Symptoms ◽

Polygenic Risk Score ◽

Polygenic Risk

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A Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men

10.1101/2021.04.25.21256083 ◽

2021 ◽

Author(s):

Hasanga D. Manikpurage ◽

Aida Eslami ◽

Nicolas Perrot ◽

Zhonglin Li ◽

Christian Couture ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Risk Score ◽

Predictive Accuracy ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Artery Disease ◽

Genetically Determined

ABSTRACTBackgroundSeveral risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.MethodsA PRSCAD including the weighted effects of >1.14 million SNPs associated with CAD was calculated in UK Biobank (n=408,422), using LDPred. Cox regressions were performed, stratified by age quartiles and sex, for incident MI and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).ResultsFrom 7,746 incident MI cases and 393,725 controls, hazard ratio (HR) for MI reached 1.53 (95% CI [1.49-1.56], p=2.69e-296) per standard deviation (SD) increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction p=0.002), particularly in those aged between 40-51 years (HR=2.00, 95% CI [1.86-2.16], p=1.93e-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02=0.199, 95% CI [0.157-0.248] and NRI>0=0.602, 95% CI [0.525-0.683]). From 23,982 deaths, HR for mortality was 1.08 (95% CI [1.06-1.09], p=5.46e-30) per SD increase of PRSCAD, with a stronger association in men (interaction p=1.60e-6).ConclusionOur PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40-51 years. PRS could optimize the identification and management of individuals at risk for CAD.

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Ageing on the autism spectrum: A 4-year follow-up study of mental health and quality of life in autistic adults

10.22541/au.162912521.10897548/v1 ◽

2021 ◽

Author(s):

Dr Amanda Roestorf ◽

Patricia Howlin ◽

Dermot M. Bowler

Keyword(s):

Quality Of Life ◽

Mental Health ◽

Autistic Traits ◽

Autism Spectrum ◽

Health Conditions ◽

Depression Symptoms ◽

Mental Health Conditions ◽

Autistic Adults

Background: Poor mental health is known to adversely affect functional abilities, social isolation and quality of life (QoL). It is, therefore, crucial to consider the long-term impacts of mental health conditions as autistic adults grow older. Objectives: Our objectives were to understand the extent of: (i) autistic traits, co-occurring physical and mental health conditions; (ii) age-related differences in those conditions; and (iii) their impact on everyday living and QoL. Method: Fifty-two autistic adults (aged 18-79 years) participated in the first study (T1); 28 took part in a follow-up at T2 (mean retest interval 2.5 years). Standardised self-report measures of autistic traits, mental health and QoL were completed at both time points. Results: Over half of autistic adults experienced at least one co-occurring condition, and over a third met the criteria for 3+ conditions. Depression symptoms were particularly high in autistic women. Mental and physical health problems were related to autistic traits, difficulties in everyday life, and were a strong and consistent predictor of poor QoL (T1; T2) across the lifespan. Conclusion: Our findings highlighted that mental health difficulties persisted into older age and did not reduce over time. Together, these findings raise important questions about mental health provision in adult autism.

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S24. PATHWAYS LINKING ENVIRONMENTAL RISKS, POLYGENIC RISK SCORE TO SCHIZOPHRENIA AND PSYCHOTIC EXPERIENCES IN A BRAZILIAN COHORT OF CHILDREN AND ADOLESCENTS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.090 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S39-S40

Author(s):

Lais Fonseca ◽

Gabrielle de Oliveira S V Navarro ◽

Marcos Leite Santoro ◽

Pedro M Pan ◽

Rodrigo Bressan ◽

...

Keyword(s):

Children And Adolescents ◽

Risk Score ◽

Moderated Mediation ◽

Polygenic Risk Score ◽

Psychotic Experiences ◽

Mediation Model ◽

Polygenic Risk ◽

Moderated Mediation Model ◽

P Factor

Abstract Background Polygenic risk score to schizophrenia (PRS-SZ) provides a liability measure summarizing each genetic risk variant and the polyenviromic risk score (PERS) proposes the same regarding exposure factors to psychosis, yet few studies addressed how both scopes interplay, especially in early developmental stages. Psychotic experiences (PE) rest on the lower range of psychosis spectrum, representing an important asset to study psychotic disorders, ie. schizophrenia. However, investigators failed to find significant associations between PRS-SZ and PE in children. We hypothesize that unspecific psychopathology – also previously linked to PE – can mediate the effects of higher risk load for psychosis during neurodevelopment. Thus, our aim is to test a moderated mediation model in which PERS and general psychopathology in youths can lead to PE, prospectively, through SZ genetic liability. Methods We analyzed data from the Brazilian High-Risk Cohort for Psychiatric Disorders, a youth community sample with 2 time-points: baseline (w0) and 3year follow-up (w1), from São Paulo and Porto Alegre, both urban centers. PRS-SZ was calculated using summary statistics from the PGC and corrected for the 10 principal components of the GWAS. PE were assessed at w0 and w1 with the Community Assessment Psychotic Experiences – CAPE and trained psychologists rated the reliability of students’ answers. The Development and Well-Being Assessment – DAWBA, a structured interview with a transdiagnostic approach, was used to extract a general factor for psychopathology (P-factor) on w0. Latent variables for PE and P-factor were generated through confirmatory factor analysis yielding good model fits. We calculated PERS on w0, as validated, with birth season, urbanicity, cannabis use, paternal age, obstetric/perinatal complications and physical/sexual abuse, neglect or parental loss/separation. Last, we built a moderated mediation diagram based on model 15 of Haye’s PROCESS builder on SPSS: (X) PERS > (M) P-factor > (Y) PE w1, with (V) PRS-SZ as a moderator for PERS > PE and P-factor > PE. Age, sex, site and PE w0 were covariates. Results 2,511 students (6–14 y/o, mean=10.2 ± 1.9, 53% male) completed the w0 assessment and 2,010 the follow-up (mean=13.5 y/o ± 1.9). In our moderated mediation model, P-factor emerged as a full mediator between PERS and PE w1 (B=.324, BootLL–UL CI=.138 to .553). We found PRS-SZ provided a significant moderation effect on the P-factor > PE relation (M*V=.053, R2-chng=.003, p=.037), with the moderator effects of the focal predictor rising considerably according to values of PRS-SZ: p16 (B=.047, p=.192), p50 (B=.099, p=.000) and p84 (B=.153, p=.000). PRS-SZ did not moderate PERS > PE separately (X*V=.016, R2-chng=.001, p=.974). However, conditional indirect coefficients for the complete model were also significant for higher PRS-SZ levels: p16 (B=.143, BootLL–UL CI=-.072 to .389), p50 (B=.304, BootLL–UL CI=.126 to .529) and p84 (B=.470, BootLL–UL CI=.197 to .814). Discussion Our findings suggest environmental risk factors and intermediate phenotypes – namely unspecific non-psychotic psychopathology – can play crucial and intertwined roles in children and adolescents with higher genetic liability to SZ. Moreover, the moderation effects of PRS-SZ imply the existence of thresholds for those relations. The non-clinical nature and age of our sample could explain the low effect sizes. Next steps would include additional phenotypic tracks, such as cognition and social functionality – both previously connected to PRS-SZ as well. We hope our results can help disentangle the genetic and environmental trajectories bonding SZ proneness and PE, and possibly contribute to risk assessment in youths, especially among vulnerable populations.

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