Genetic Risk for Psychiatric Disorders Linked With Living in Urban Areas

Young Caucasian woman watching sunset.
Researchers in the United Kingdom analyzed genetic and phenotype data from the UK Biobank of 385,793 individuals aged 37 to 73 years.

High genetic risk for psychiatric disorders may impact individuals’ desire to live in cities or rural areas, even without diagnosis of mental illness, researchers found in a study published in JAMA Psychiatry.

Researchers in the United Kingdom analyzed genetic and phenotype data from the UK Biobank (UKB) of 385,793 individuals (54% women) of European ancestry aged 37 to 73 years. The researchers selected imputed single-nucleotide variants (SNVs) minor allele frequency greater than 0.01 and information score greater than 0.6.

They excluded individuals with missingness greater than 0.01, sex discordance, and relatedness and they examined participants’ address history from 1931 to 2011. Additional address history was collected from participants and their registration with a primary care physician. The researchers used land cover maps to identify urban and rural areas by postcode.

Researchers found that being in the 45 to 55 year age group and having polygenic risk scores (PRS) 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 (ASD) (35 people/km2; 95% CI, 25-45 people/km2) were linked with living in areas of higher population density.

People with PRS for schizophrenia tended to be born in urban environments (β = 37 people/km2; 95% CI, 19-55 people/km2; P = 8 × 10−5). Attention deficit/hyperactivity disorder (ADHD) PRS was linked with more rural areas (age 35 to 45 years −31 people/km2; 95% CI, −42 to −20 people/km2).

When they examined migration patterns, the researchers found that individuals with PRS for schizophrenia, bipolar disorder, anorexia nervosa, and ASD and those with reduced PRS for ADHD tended to choose to move from rural areas to urban areas.

SNV-based heritability of birth population density was 0.074 and 0.066 for the current population density.

Adjusting for 20 ancestry informed principal components, UKB batch, age, and sex, population density was linked in genetics correlation with schizophrenia (rg = 0.21; P =8 × 10−10), bipolar disorder (rg = 0.27; P =6 × 10−11), and ASD (rg = 0.31; P =3 × 10−10) and remained the same when adjusting for education levels and attenuated after adjusting for socioeconomic status and educational attainment via the UKB’s Townsend Deprivation Index.

When they analyzed data utilizing Mendelian randomization, the researchers found that SNVs indicating schizophrenia (bxy = 33; P =7 × 10−9) and bipolar disorder (bxy = 48; P =.001) were associated with current population density.

The researchers said that pleiotropic variants could impact risk of mental disorders and choice of residence, symptoms or traits could prompt the moves, or behaviors associated with psychiatric disorders, such as risk taking and creativity, could prompt the moves.

According to the researchers, in the UKB, population density is linked with deprivation and educational levels, impacting generalization.


Maxwell JM, Coleman JRI, Breen G, Vassos E. Association between genetic risk for psychiatric disorders and the probability of living in urban settings. JAMA Psychiatry. Published online October 27, 2021. doi: 10.1001/jamapsychiatry.2021.2983