Genetic Risk of Mental Health Conditions May Influence Where People Choose to Live

Summary: Genetic risk factors for certain mental health disorders may impact people’s decisions regarding whether to live in urban areas or rural areas, a new study reports.

Source: King’s College London

Living in cities has been highlighted as an environmental risk factor for schizophrenia and, to a lesser extent, other mental health conditions. However, few studies have explored genetic effects on the choice of residence.

New research, published in JAMA Psychiatry, challenges the proposals that city-living is a simple environmental risk factor for schizophrenia or that those with diagnosed mental health conditions move to cities seeking better access to healthcare services. Instead, the research suggests that genetic liability to a variety of mental health conditions may affect an individual’s choice of residence.

The research was part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre.

First author Jessye Maxwell, PhD candidate from Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said: “Our research shows that at some level an individual’s genes select their environment and that the relationship between environmental and genetic influences on mental health is interrelated. This overlap needs to be considered when developing models to predict the risk of people developing mental health conditions in the future.

“Importantly the majority of those people in our analysis did not have a diagnosed mental health condition so we are showing that across the UK adult population this genetic risk for mental health conditions plays a role in the environment that people live.”

Using the genetic data from 385,793 UK Biobank participants aged 37 to 73, the researchers calculated the polygenic risk score (PRS) for each individual for different mental health conditions. The PRS assesses the genetic liability across the entire genome of each individual rather than analysing liability at the level of individual genes.

The relationship to where people currently live and where they have moved to was analysed using address history and geographical distribution of population density in the UK based on census data from 1931 to 2011.

The study revealed higher genetic risks of schizophrenia, bipolar disorder, anorexia and autism spectrum disorder and lower genetic risk for ADHD in those who moved from rural to urban areas, compared to those who stayed in rural areas.

Lead author, Dr Evangelos Vassos, Research Fellow at the IoPPN, King’s College London and Consultant Psychiatrist said: “Our study provides further evidence that genetic liability to a variety of mental disorders may contribute to the choice of a person’s environment. The findings do not negate the important role that environment plays in the development of mental health conditions but it does suggest that we need more integrated approaches when exploring the causes of psychiatric disorders.

“The findings on ADHD are particularly interesting as, unlike other mental health conditions, people at low genetic risk of developing ADHD appear to have the tendency to move to cities. This observation highlights the importance of examining the low end of the distribution of genetic liability and not only focusing on people at high risk. More research is needed to understand the possible reasons behind this distinction.”

The study was carried out by researchers from the Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London.

Census data was provided through www.VisionofBritain.org.uk and uses statistical material which is copyright of the Great Britain Historical GIS Project, Humphrey Southall and the University of Portsmouth.

Abstract

Association Between Genetic Risk for Psychiatric Disorders and the Probability of Living in Urban Settings

Importance Urban residence has been highlighted as an environmental risk factor for schizophrenia and, to a lesser extent, several other psychiatric disorders. However, few studies have explored genetic effects on the choice of residence.

Objective

To investigate whether individuals with genetic predisposition to a range of psychiatric disorders have an increased likelihood to live in urban areas.

Design, Setting, and Participants

A cross-sectional retrospective cohort study including genotypes, address history, and geographic distribution of population density in the UK based on census data from 1931-2011 was conducted. Polygenic risk score (PRS) analyses, genome-wide association studies, genetic correlation, and 2-sample mendelian randomization analyses were applied to 385 793 UK Biobank participants with self-reported or general practitioner registration–based address history. The study was conducted from February 2018 to May 2021, and data analysis was performed from April 2018 to May 2021.

Main Outcomes and Measures

Population density of residence at different ages and movement during the life span between urban and rural environments.

Results

In this cohort study of 385 793 unrelated UK Biobank participants (207 963 [54%] were women; age, 37-73 years; mean [SD], 56.7 [8] years), PRS analyses showed significant associations with higher population density across adult life (age 25 to >65 years) reaching highest significance at the 45- to 55-year age group for schizophrenia (88 people/km²; 95% CI, 65-98 people/km²), bipolar disorder (44 people/km²; 95% CI, 34-54 people/km²), anorexia nervosa (36 people/km²; 95% CI, 22-50 people/km²), and autism spectrum disorder (35 people/km²; 95% CI, 25-45 people/km²). The schizophrenia PRS was also significantly associated with higher birthplace population density (37 people/km²; 95% CI, 19-55 people/km²; P = 8 × 10⁻⁵).

Attention-deficit/hyperactivity disorder PRS was significantly associated with reduced population density in adult life (−31 people/km²; 95% CI, −42 to −20 people/km² at age 35-45 years). Individuals with higher PRS for schizophrenia, bipolar disorder, anorexia nervosa, and autism spectrum disorder and lower PRS for attention-deficit/hyperactivity disorder preferentially moved from rural environments to cities (difference in PRS with Tukey pairwise comparisons for schizophrenia: 0.05; 95% CI, 0.03 to 0.60; bipolar disorder: 0.10; 95% CI, 0.08 to 0.13; anorexia nervosa: 0.05; 95% CI, 0.03 to 0.07; autism spectrum disorder: 0.04; 95% CI 0.03 to 0.06; and attention-deficit/hyperactivity disorder: −0.09, 95% CI, −0.12 to −0.06). Genetic correlation results were largely consistent with PRS analyses, whereas mendelian randomization provided support for associations between schizophrenia and bipolar disorder and living in high population-density areas.

Conclusions and Relevance

These findings suggest that a high genetic risk for a variety of psychiatric disorders may affect an individual’s choice of residence. This result supports the hypothesis of genetic selection of an individual’s environment, which intersects the traditional gene-environment dichotomy.