City or Country Life? Genetic Risk for Mental Illness May Decide

High genetic risk for a range of psychiatric illnesses appears to influence individuals’ choice of urban or rural life, new research suggests.

Individuals with a genetic predisposition to schizophrenia, bipolar disorder (BD), autism spectrum disorder (ASD), or anorexia nervosa (AN) are significantly more likely to move from a rural to an urban setting, whereas those at high genetic risk for attention deficit hyperactivity disorder (ADHD) were more likely to do the opposite.

The findings held even in those at high genetic risk who had never been diagnosed with a psychiatric disorder, highlighting a genetic factor that previous research linking urban living to mental illness has not explored.

Dr Evangelos Vassos

“It’s not as simple as saying that urban environment is responsible for schizophrenia and everyone should move out of urban environments and they will be safe,” study investigator Evangelos Vassos, MD, PhD, senior clinical research fellow at King’s College London, UK, and a consulting psychiatrist, told Medscape Medical News. “If you are genetically predisposed to schizophrenia, you will still be predisposed schizophrenia even if you move.”

The study was published online October 27 in JAMA Psychiatry.

Genetic Influence

The study results don’t rule out environmental influence, but offers evidence that the migration pattern researchers have tracked for years may have a multifactorial explanation.

“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,” Jessye Maxwell, MSc, lead author and a PhD candidate in psychiatry at King’s College, said in a statement. “This overlap needs to be considered when developing models to predict the risk of people developing mental health conditions in the future.”

For the study, the investigators calculated polygenic risk scores (PRS) of different psychiatric illnesses for 385,793 UK Biobank participants aged 37-73. PRS analyzes genetic information across a person’s entire genome, rather than by individual genes.

They used address history and UK census records from 1931-2011 to map population density over time.

PRS analyses showed significant associations with higher population density throughout adulthood, reaching highest significance between age 45-55-years for schizophrenia (88 people/km2; 95% CI, 65-98 people/km2), BD (44 people/km2; 95%CI, 34-54 people/km2), AN (36 people/km2; 95%CI, 22-50 people/km2), and ASD (35 people/km2; 95%CI, 25-45 people/km2).

When they compared those who were born and stayed in rural or suburban areas to their counterparts who moved from those areas to cities, they found the odds of moving to urban areas ranged from 5% among people at high genetic risk for schizophrenia to 13% of those with a high risk for BD. Only people at high risk for ADHD were more likely to move to rural areas.

However, the study is not without its limitations. Only people of European descent were included, family medical history was unavailable for some participants, and only about 50,000 people had a lifetime diagnosis of mental illness, which is not representative of the general population.

“Convincing Evidence”

Still, the research adds another piece of the puzzle scientists seek to solve about where people live and mental illness risk, said Jordan DeVylder, PhD, associate professor of social work at Fordham University, New York City, who commented on the study for Medscape Medical News.

Dr Jordan DeVylder

DeVylder, who has also published research on the topic but was not part of the current study, noted that urban living has long thought to be among the most consistent environmental risk factor for psychosis. However, he noted, “this association can also be explained by genetic selection, in which the same genes that predispose one to schizophrenia also predispose one to choose urban living.”

“This study presents the most convincing evidence to date that genetics have a major role in this association, at least in the countries where this association between urban living and psychosis exists,” he said.

The study was funded by National Institute for Health Research, Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The authors and DeVylder have disclosed no relevant financial relationships.

JAMA Psych. Published online October 27, 2021. Abstract

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