Adults with a higher genetic risk for schizophrenia tend to live in urban areas, according to a study in JAMA Psychiatry involving a half-million people.
The finding, based on 4 community-based samples, suggests a need to factor genetics into the social stress model for schizophrenia, researchers noted.
“In all 4 nonclinical cohorts, genetic risk for schizophrenia was associated with greater population density of the postcode of residence beyond what could be explained by socioeconomic status of the area,” researchers wrote. “Our results show that the geographic distribution of the genetic risk for schizophrenia is not uniform and that participants with higher genetic risk levels live in areas with higher population density over what is expected by chance.”
The cross-sectional study included 504,130 adults from 4 communities in Australia, the United Kingdom, and the Netherlands. Genetic loading for schizophrenia was significantly higher in people who lived in more densely populated areas, researchers reported. Mendelian randomization, they added, suggested a causal association between schizophrenia and the choice to live in urban areas.
“Our findings support the notion that the increased schizophrenia prevalence in urbanized areas is not only owing to the environmental stressors of the city or other putative risk factors associated with urbanicity (eg, increased risk of infection, low vitamin D levels, and substance abuse) but also on the genetic risk for the disease,” researchers concluded.
In a JAMA Psychiatry editorial, Hannah E. Jongsma, MPH, PhD, and Peter B. Jones, MD, PhD, of the University of Cambridge, United Kingdom, called the study an important “genetic epidemiological tour de force.” But they warned against concluding gene-environment selection is the cause of the link between urban living and schizophrenia.
They pointed out that polygenic risk scores for schizophrenia used in the study account for just an eighth of schizophrenia heritability—and their predictive value is even lower in black people.
“Thus, the present study can address only part of the conundrum concerning schizophrenia in cities,” the editorialists wrote. “This limitation is inherent to the polygenic risk score, and this study illustrates the potential that could be unlocked with a more representative polygenic risk score by demonstrating what can already be done with quite a limited instrument.”