|
|
| PMID |
|
|
| TITLE |
|
| Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior. |
|
| ABSTRACT |
|
| Importance |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. |
| Objectives |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. |
| Design, Setting, and Participants |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). |
| Main Outcome and Measures |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. |
| Results |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. |
| Conclusions and Relevance |
|
| Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2017/10/06 06:00 |
| medline |
2017/12/14 06:00 |
| entrez |
2017/10/06 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Tielbeek JJ |
|
Tielbeek |
Jorim J |
JJ |
|
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. |
| Johansson A |
|
Johansson |
Ada |
A |
|
Department of Psychology, Faculty of Arts, Psychology, and Theology, Åbo Akademi University, Turku, Finland. |
| Polderman TJC |
|
Polderman |
Tinca J C |
TJC |
|
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
| Rautiainen MR |
|
Rautiainen |
Marja-Riitta |
MR |
|
Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. |
| Jansen P |
|
Jansen |
Philip |
P |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. |
| Taylor M |
|
Taylor |
Michelle |
M |
|
Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, England. |
| Tong X |
|
Tong |
Xiaoran |
X |
|
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing. |
| Lu Q |
|
Lu |
Qing |
Q |
|
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing. |
| Burt AS |
|
Burt |
Alexandra S |
AS |
|
Department of Psychology, Michigan State University, East Lansing. |
| Tiemeier H |
|
Tiemeier |
Henning |
H |
|
Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands. |
| Viding E |
|
Viding |
Essi |
E |
|
Division of Psychology and Language Sciences, University College London, London, England. |
| Plomin R |
|
Plomin |
Robert |
R |
|
Division of Psychology and Language Sciences, University College London, London, England. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. |
| Heath AC |
|
Heath |
Andrew C |
AC |
|
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri. |
| Madden PAF |
|
Madden |
Pamela A F |
PAF |
|
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri. |
| Montgomery G |
|
Montgomery |
Grant |
G |
|
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. |
| Beaver KM |
|
Beaver |
Kevin M |
KM |
|
Center for Social and Humanities Research, King Abdulaziz University, Jeddah, Saudi Arabia. |
| Waldman I |
|
Waldman |
Irwin |
I |
|
Psychology Department, Emory University, Atlanta, Georgia. |
| Gelernter J |
|
Gelernter |
Joel |
J |
|
Veterans Affairs (VA) Connecticut Healthcare Center, New Haven. |
| Kranzler HR |
|
Kranzler |
Henry R |
HR |
|
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. |
| Farrer LA |
|
Farrer |
Lindsay A |
LA |
|
Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts. |
| Perry JRB |
|
Perry |
John R B |
JRB |
|
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, England. |
| Munafò M |
|
Munafò |
Marcus |
M |
|
Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, England. |
| LoParo D |
|
LoParo |
Devon |
D |
|
Psychology Department, Emory University, Atlanta, Georgia. |
| Paunio T |
|
Paunio |
Tiina |
T |
|
Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. |
| Tiihonen J |
|
Tiihonen |
Jari |
J |
|
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland. |
| Mous SE |
|
Mous |
Sabine E |
SE |
|
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands. |
| Pappa I |
|
Pappa |
Irene |
I |
|
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands. |
| de Leeuw C |
|
de Leeuw |
Christiaan |
C |
|
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
| Watanabe K |
|
Watanabe |
Kyoko |
K |
|
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. |
| Hammerschlag AR |
|
Hammerschlag |
Anke R |
AR |
|
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. |
| Salvatore JE |
|
Salvatore |
Jessica E |
JE |
|
Department of Psychology and the Virginia Institute for Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond. |
| Aliev F |
|
Aliev |
Fazil |
F |
|
Faculty of Business, Karabuk University, Karabuk, Turkey. |
| Bigdeli TB |
|
Bigdeli |
Tim B |
TB |
|
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond. |
| Dick D |
|
Dick |
Danielle |
D |
|
Department of Psychology, African American Studies, and Human & Molecular Genetics, Virginia Commonwealth University, Richmond. |
| Faraone SV |
|
Faraone |
Stephen V |
SV |
|
Department of Neuroscience and Physiology, Psychiatric Genetic Epidemiology and Neurobiology Laboratory, SUNY Upstate Medical University, Syracuse, New York. |
| Popma A |
|
Popma |
Arne |
A |
|
Department of Child and Adolescent Psychiatry, VU University Medical Center, Amsterdam, the Netherlands. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. |
| Posthuma D |
|
Posthuma |
Danielle |
D |
|
Department of Clinical Genetics, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center, Amsterdam, the Netherlands. |
|
Broad Antisocial Behavior Consortium collaborators |
|
|
|
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 74 |
| ISSUE: 12 |
| TITLE: JAMA psychiatry |
| ISOABBREVIATION: JAMA Psychiatry |
| YEAR: 2017 |
| MONTH: 12 |
| DAY: 01 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2168-6238 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: JAMA Psychiatry |
| COUNTRY: United States |
| ISSNLINKING: 2168-622X |
| NLMUNIQUEID: 101589550 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
| Research Support, N.I.H., Extramural |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| ErratumIn |
JAMA Psychiatry. 2018 Mar 1;75(3):303 |
29365011 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| MC_UU_12013/6 |
Medical Research Council |
United Kingdom |
| G0901245 |
Medical Research Council |
United Kingdom |
| K01 DA033346 |
NIDA NIH HHS |
United States |
| G19/2 |
Medical Research Council |
United Kingdom |
| K01 AA024152 |
NIAAA NIH HHS |
United States |
| MR/M021475/1 |
Medical Research Council |
United Kingdom |
| G0500079 |
Medical Research Council |
United Kingdom |
| F32 AA022269 |
NIAAA NIH HHS |
United States |
| MC_UU_12015/2 |
Medical Research Council |
United Kingdom |
| MC_PC_15018 |
Medical Research Council |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Antisocial Personality Disorder |
psychology |
| Child |
psychology |
| Conduct Disorder |
psychology |
| Environment |
psychology |
| Female |
psychology |
| Finland |
epidemiology |
| Genetic Variation |
epidemiology |
| Genome-Wide Association Study |
epidemiology |
| Humans |
epidemiology |
| Male |
epidemiology |
| Middle Aged |
epidemiology |
| Multifactorial Inheritance |
epidemiology |
| Sex Factors |
epidemiology |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
