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

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. To investigate whether individuals with genetic predisposition to a rang...

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Vydané v:	JAMA psychiatry (Chicago, Ill.) Ročník 78; číslo 12; s. 1355
Hlavní autori:	Maxwell, Jessye M, Coleman, Jonathan R I, Breen, Gerome, Vassos, Evangelos
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.12.2021
Predmet:	Adult Aged Cross-Sectional Studies Databases, Genetic Female Genetic Predisposition to Disease - genetics Genome-Wide Association Study Humans Male Mendelian Randomization Analysis Mental Disorders - epidemiology Mental Disorders - genetics Middle Aged Multifactorial Inheritance Neighborhood Characteristics - statistics & numerical data Retrospective Studies Risk United Kingdom - epidemiology Urban Population - statistics & numerical data United Kingdom
ISSN:	2168-6238, 2168-6238
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Abstract	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. To investigate whether individuals with genetic predisposition to a range of psychiatric disorders have an increased likelihood to live in urban areas. 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. Population density of residence at different ages and movement during the life span between urban and rural environments. 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. 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.
AbstractList	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.ImportanceUrban 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.To investigate whether individuals with genetic predisposition to a range of psychiatric disorders have an increased likelihood to live in urban areas.ObjectiveTo investigate whether individuals with genetic predisposition to a range of psychiatric disorders have an increased likelihood to live in urban areas.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.Design, Setting, and ParticipantsA 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.Population density of residence at different ages and movement during the life span between urban and rural environments.Main Outcomes and MeasuresPopulation density of residence at different ages and movement during the life span between urban and rural environments.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.ResultsIn 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.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.Conclusions and RelevanceThese 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. 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. To investigate whether individuals with genetic predisposition to a range of psychiatric disorders have an increased likelihood to live in urban areas. 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. Population density of residence at different ages and movement during the life span between urban and rural environments. 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. 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.
Author	Maxwell, Jessye M Breen, Gerome Coleman, Jonathan R I Vassos, Evangelos
Author_xml	– sequence: 1 givenname: Jessye M surname: Maxwell fullname: Maxwell, Jessye M organization: National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, United Kingdom – sequence: 2 givenname: Jonathan R I surname: Coleman fullname: Coleman, Jonathan R I organization: National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, United Kingdom – sequence: 3 givenname: Gerome surname: Breen fullname: Breen, Gerome organization: National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, United Kingdom – sequence: 4 givenname: Evangelos surname: Vassos fullname: Vassos, Evangelos organization: National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, United Kingdom
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References	34851375 - JAMA Psychiatry. 2021 Dec 1;78(12):1395. doi: 10.1001/jamapsychiatry.2021.3677.
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SubjectTerms	Adult Aged Cross-Sectional Studies Databases, Genetic Female Genetic Predisposition to Disease - genetics Genome-Wide Association Study Humans Male Mendelian Randomization Analysis Mental Disorders - epidemiology Mental Disorders - genetics Middle Aged Multifactorial Inheritance Neighborhood Characteristics - statistics & numerical data Retrospective Studies Risk United Kingdom - epidemiology Urban Population - statistics & numerical data
Title	Association Between Genetic Risk for Psychiatric Disorders and the Probability of Living in Urban Settings
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