Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort

Abstract Background Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. Methods We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994–1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. Results Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06–1.33), depression PRS (OR = 1.20, 95% CI = 1.08–1.34), family history (OR = 1.25, 95% CI = 1.11–1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07–1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. Conclusion Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

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O8.1. ASSOCIATION BETWEEN GENETIC AND ENVIRONMENTAL RISK FOR SCHIZOPHRENIA DURING UPBRINGING: FINDINGS FROM A LONGITUDINAL COHORT STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.042 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S18-S19

Author(s):

Joanne Newbury ◽

Louise Arseneault ◽

Avshalom Caspi ◽

Terrie Moffitt ◽

Candice Odgers ◽

...

Keyword(s):

Residential Mobility ◽

Environmental Risk ◽

Genetic Risk ◽

Environmental Risks ◽

Risk Scores ◽

Psychiatric History ◽

Neighborhood Disorder ◽

Crime Victimization ◽

Downward Mobility ◽

Reverse Causation

Abstract Background Associations of environmental exposures such as urban upbringing, deprivation and crime victimization with psychosis are well-established. An enduring question, however, is whether associations reflect a causal process. Emerging evidence using polygenic risk scores (PRS) suggests reverse causation, with adults at higher genetic risk for schizophrenia being more likely to live in crowded and deprived areas. This process could occur due to the downward mobility of individuals at higher genetic risk for schizophrenia into more disadvantaged environments. However, the handful of studies on this topic to date have typically focused on environmental conditions during adulthood and have typically examined only macro-level environmental features (e.g., urbanicity). Methods We examined associations between two measures of genetic risk (PRS for schizophrenia and family psychiatric history) with multiple features of children’s family-, neighborhood-, and wider- environments during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2,232 British twins born in 1994–1995 and followed to age 18 (with 93% retention). Environmental risk factors were measured from early childhood to late adolescence, and included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, family poverty, residential mobility, and crime victimization. At age 18, participants were privately interviewed about psychotic experiences (e.g., hallucinations and delusions) occurring since age 12. Results Children with higher schizophrenia PRS and a greater family psychiatric history were exposed to a wide range of riskier environments during upbringing. For schizophrenia PRS, associations were significant at p<0.05 for neighborhood crime (OR=1.16, 95% CI=1.04–1.29), neighborhood disorder (OR=1.16, 95% CI=1.04–1.30), family poverty (OR=1.12, 95% CI=1.10–1.25) and residential mobility (OR=1.24, 95% CI=1.10–1.40). In contrast, for family psychiatric history, associations were significant at p<0.05 for family poverty (OR=1.26, 95% CI=1.11–1.42), residential mobility (OR=1.32, 95% CI=1.17–1.50), and crime victimization (OR=1.24, 95% CI=1.12–1.38). However, associations between environmental risks and adolescent psychotic experiences were essentially unchanged after controlling for schizophrenia PRS and family psychiatric history. Discussion Consistent with a degree of reverse causation, we found that children with higher genetic risk for schizophrenia also experienced riskier environments during upbringing. In particular, children at higher genetic risk were more likely to grow up in dangerous neighborhoods, poorer families, and move houses more frequently across childhood. However, genetic risk for schizophrenia (using polygenic risk scores and family psychiatric history) does not appear to confound associations of environmental risks with early expressions of psychosis. Nevertheless, future research into environmental conditions and psychosis should acknowledge and ideally examine the possibility of reverse-causation due to the downward mobility of individuals at higher genetic risk for schizophrenia into riskier environments.

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In the eye of the beholder: Perceptions of neighborhood adversity and psychotic experiences in adolescence

Development and Psychopathology ◽

10.1017/s0954579417001420 ◽

2017 ◽

Vol 29 (5) ◽

pp. 1823-1837 ◽

Cited By ~ 8

Author(s):

Joanne B. Newbury ◽

Louise Arseneault ◽

Avshalom Caspi ◽

Terrie E. Moffitt ◽

Candice L. Odgers ◽

...

Keyword(s):

Confidence Interval ◽

Psychotic Symptoms ◽

Neighborhood Disorder ◽

Psychotic Experiences ◽

Neighborhood Conditions ◽

Personal Perceptions ◽

Nationally Representative ◽

Using Data ◽

Longitudinal Twin Study

AbstractAdolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.

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High genetic risk scores of SLIT3, PLEKHA5 and PPP2R2C variants increased insulin resistance and interacted with coffee and caffeine consumption in middle-aged adults

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2018.09.009 ◽

2019 ◽

Vol 29 (1) ◽

pp. 79-89 ◽

Cited By ~ 4

Author(s):

J.W. Daily ◽

M. Liu ◽

S. Park

Keyword(s):

Insulin Resistance ◽

Genetic Risk ◽

Risk Scores ◽

Middle Aged ◽

Caffeine Consumption ◽

Genetic Risk Scores ◽

High Genetic Risk ◽

Middle Aged Adults

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CME Exam 3: Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease

Gastroenterology ◽

10.1053/j.gastro.2018.06.026 ◽

2018 ◽

Vol 155 (1) ◽

pp. e25-e26

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Diet Quality ◽

Genetic Risk ◽

Fatty Liver Disease ◽

Liver Fat ◽

Risk Scores ◽

Nonalcoholic Fatty Liver ◽

High Genetic Risk

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Multiomic blood correlates of genetic risk identify presymptomatic disease alterations

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2001429117 ◽

2020 ◽

Vol 117 (35) ◽

pp. 21813-21820

Author(s):

Michael Wainberg ◽

Andrew T. Magis ◽

John C. Earls ◽

Jennifer C. Lovejoy ◽

Nasa Sinnott-Armstrong ◽

...

Keyword(s):

Biological Networks ◽

Genetic Risk ◽

Complex Traits ◽

Clinical Laboratory ◽

Clinical Symptoms ◽

Association Studies ◽

Risk Scores ◽

Genome Wide Association Studies ◽

High Genetic Risk ◽

Genetic And Environmental Factors

Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.

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Childhood socioeconomic status moderates genetic predisposition for peak smoking

10.1101/336834 ◽

2018 ◽

Cited By ~ 1

Author(s):

Laura Bierut ◽

Pietro Biroli ◽

Titus J. Galama ◽

Kevin Thom

Keyword(s):

At Risk ◽

Socioeconomic Status ◽

Genetic Predisposition ◽

Genetic Variants ◽

Genetic Risk ◽

Risk Scores ◽

Low Ses ◽

High Genetic Risk ◽

Childhood Socioeconomic Status ◽

The U.S

AbstractSmoking is the leading cause of preventable disease and death in the U.S., and it is strongly influenced both by genetic predisposition and childhood socioeconomic status (SES). Using genetic variants exhibiting credible and robust associations with smoking, we construct polygenic risk scores (PGS) and evaluate whether childhood SES mediates genetic risk in determining peak-cigarette consumption in adulthood. We find a substantial protective effect of childhood SES for those genetically at risk of smoking: adult smokers who grew up in high-SES households tend to smoke roughly the same amount of cigarettesper day at peak (∼ 23 for low and ∼ 25 for high genetic risk individuals, or about 8%more), while individuals from low-SES backgrounds tend to smoke substantially more ifgenetically at risk (∼ 25 for low and ∼ 32 for high genetic risk individuals, or about 28% more).

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Correlations between fMRI activation and individual psychotic symptoms in un-medicated subjects at high genetic risk of schizophrenia

BMC Psychiatry ◽

10.1186/1471-244x-7-61 ◽

2007 ◽

Vol 7 (1) ◽

Cited By ~ 35

Author(s):

Heather C Whalley ◽

Viktoria-Eleni Gountouna ◽

Jeremy Hall ◽

Andrew McIntosh ◽

Marie-Claire Whyte ◽

...

Keyword(s):

Genetic Risk ◽

Psychotic Symptoms ◽

High Genetic Risk

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Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease

Gastroenterology ◽

10.1053/j.gastro.2018.03.038 ◽

2018 ◽

Vol 155 (1) ◽

pp. 107-117 ◽

Cited By ~ 43

Author(s):

Jiantao Ma ◽

Rachel Hennein ◽

Chunyu Liu ◽

Michelle T. Long ◽

Udo Hoffmann ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Diet Quality ◽

Genetic Risk ◽

Fatty Liver Disease ◽

Liver Fat ◽

Risk Scores ◽

Nonalcoholic Fatty Liver ◽

High Genetic Risk

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Sexual Differences in Genetic Predisposition of Coronary Artery Disease

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003147 ◽

2020 ◽

Author(s):

Yunfeng Huang ◽

Qin Hui ◽

Marta Gwinn ◽

Yi-Juan Hu ◽

Arshed A. Quyyumi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Risk Scores ◽

Men And Women ◽

High Genetic Risk ◽

Genome Wide ◽

Artery Disease

Background - The genomic structure that contributes to the risk of coronary artery disease (CAD) can be evaluated as a risk score of multiple variants. However, sex differences have not been fully examined in applications of genetic risk score of CAD. Methods - Using data from the UK Biobank, we constructed a CAD genetic risk score based on all known loci, three mediating trait-based (blood pressure, lipids, body mass index) sub-scores, and a genome-wide polygenic risk score based on 1.1 million variants. The differences in genetic associations with prevalent and incident CAD between men and women were investigated among 317,509 unrelated individuals of European ancestry. We also assessed interactions with sex for 161 individual loci included in the comprehensive genetic risk score. Results - For both prevalent and incident CAD, the associations of comprehensive and genome-wide genetic risk scores were stronger among men than women. Using a score of 161 loci, we observed a 2.4 times higher risk for incident CAD comparing men with high genetic risk to men with low genetic risk, but an 80 percent greater risk comparing women with high genetic risk to women with low genetic risk. (interaction p=0.002). Of the three sub-scores, the blood pressure-associated sub-score exhibited sex differences (interaction p=0.0004 per SD increase in sub-score). Analysis of individual variants identified a novel gene-sex interaction at locus 21q22.11 . Conclusions - Sexual differences in genetic predisposition should be considered in future studies of coronary artery disease, and genetic risk scores should not be assumed to perform equally well in men and women.

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