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PMID |
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TITLE |
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Association Between Population Density and Genetic Risk for Schizophrenia. |
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ABSTRACT |
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Importance |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. |
Objective |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. |
Design, Setting, and Participants |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. |
Exposures |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models. |
Main Outcomes and Measures |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models. Population density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested. |
Results |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models. Population density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested. The QIMR participants (15 544; 10 197 [65.6%] women; mean [SD] age, 54.4 [13.2] years) living in more densely populated areas (people per square kilometer) had a higher genetic loading for schizophrenia (r2 = 0.12%; P = 5.69 × 10-5), a result that was replicated across all 3 other cohorts (UKB: 345 246; 187 469 [54.3%] women; age, 65.7 [8.0] years; NTR: 11 212; 6727 [60.0%] women; age, 48.6 [17.5] years; and QSKIN: 15 726; 8602 [54.7%] women; age, 57.0 [7.9] years). This genetic association could account for 1.7% (95% CI, 0.8%-3.2%) of the schizophrenia risk. Estimates from MR analyses performed in the UKB sample were significant (b = 0.049; P = 3.7 × 10-7 using GSMR), suggesting that the genetic liability to schizophrenia may have a causal association with the tendency to live in urbanized locations. |
Conclusions and Relevance |
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Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models. Population density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested. The QIMR participants (15 544; 10 197 [65.6%] women; mean [SD] age, 54.4 [13.2] years) living in more densely populated areas (people per square kilometer) had a higher genetic loading for schizophrenia (r2 = 0.12%; P = 5.69 × 10-5), a result that was replicated across all 3 other cohorts (UKB: 345 246; 187 469 [54.3%] women; age, 65.7 [8.0] years; NTR: 11 212; 6727 [60.0%] women; age, 48.6 [17.5] years; and QSKIN: 15 726; 8602 [54.7%] women; age, 57.0 [7.9] years). This genetic association could account for 1.7% (95% CI, 0.8%-3.2%) of the schizophrenia risk. Estimates from MR analyses performed in the UKB sample were significant (b = 0.049; P = 3.7 × 10-7 using GSMR), suggesting that the genetic liability to schizophrenia may have a causal association with the tendency to live in urbanized locations. The results of this study appear to support the hypothesis that individuals with increased genetic risk tend to live in urban/dense areas and suggest the need to refine the social stress model for schizophrenia by including genetics as well as possible gene-environment interactions. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
pubmed |
2018/06/25 06:00 |
medline |
2019/10/02 06:00 |
entrez |
2018/06/25 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Colodro-Conde L |
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Colodro-Conde |
Lucía |
L |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Couvy-Duchesne B |
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Couvy-Duchesne |
Baptiste |
B |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
Whitfield JB |
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Whitfield |
John B |
JB |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Streit F |
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Streit |
Fabian |
F |
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Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. |
Gordon S |
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Gordon |
Scott |
S |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Kemper KE |
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Kemper |
Kathryn E |
KE |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
Yengo L |
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Yengo |
Loic |
L |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
Zheng Z |
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Zheng |
Zhili |
Z |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
Trzaskowski M |
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Trzaskowski |
Maciej |
M |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
de Zeeuw EL |
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de Zeeuw |
Eveline L |
EL |
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Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
Nivard MG |
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Nivard |
Michel G |
MG |
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Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
Das M |
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Das |
Marjolijn |
M |
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Centre for BOLD Cities, Leiden-Delft-Erasmus University, Rotterdam, the Netherlands. |
Neale RE |
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Neale |
Rachel E |
RE |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
MacGregor S |
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MacGregor |
Stuart |
S |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Olsen CM |
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Olsen |
Catherine M |
CM |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Whiteman DC |
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Whiteman |
David C |
DC |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Boomsma DI |
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Boomsma |
Dorret I |
DI |
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Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
Yang J |
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Yang |
Jian |
J |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. |
Rietschel M |
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Rietschel |
Marcella |
M |
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Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. |
McGrath JJ |
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McGrath |
John J |
JJ |
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National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. |
Medland SE |
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Medland |
Sarah E |
SE |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 75 |
ISSUE: 9 |
TITLE: JAMA psychiatry |
ISOABBREVIATION: JAMA Psychiatry |
YEAR: 2018 |
MONTH: 09 |
DAY: 01 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 2168-6238 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: JAMA Psychiatry |
COUNTRY: United States |
ISSNLINKING: 2168-622X |
NLMUNIQUEID: 101589550 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
CommentIn |
JAMA Psychiatry. 2018 Sep 1;75(9):878-880 |
29936531 |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
R01 AA013326 |
NIAAA NIH HHS |
United States |
R37 AA007728 |
NIAAA NIH HHS |
United States |
R01 AA010249 |
NIAAA NIH HHS |
United States |
MC_PC_17228 |
Medical Research Council |
United Kingdom |
R01 AA007535 |
NIAAA NIH HHS |
United States |
MC_QA137853 |
Medical Research Council |
United Kingdom |
R01 AA013321 |
NIAAA NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adult |
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Aged |
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Australia |
epidemiology |
Female |
epidemiology |
Gene-Environment Interaction |
epidemiology |
Genetic Predisposition to Disease |
epidemiology |
Genome-Wide Association Study |
epidemiology |
Humans |
epidemiology |
Male |
epidemiology |
Mendelian Randomization Analysis |
epidemiology |
Middle Aged |
epidemiology |
Multifactorial Inheritance |
epidemiology |
Netherlands |
epidemiology |
Population Density |
epidemiology |
Residence Characteristics |
epidemiology |
Risk Assessment |
statistics & numerical data |
Risk Factors |
statistics & numerical data |
Schizophrenia |
genetics |
Social Class |
genetics |
United Kingdom |
epidemiology |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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