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Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101


Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

Nat Neurosci ; 21(9): 1161-1170, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150663


Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

Behav Genet ; 47(1): 11-24, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27743041


Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three separable EF components measured with a latent variable model. We also examined the relationship between genetic risk for ADHD and MDD and their respective symptom counts and lifetime diagnoses. We found no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders. However, larger sample sizes will be important in examining this relationship further.

Cognição , Função Executiva , Herança Multifatorial/genética , Transtornos Psicóticos/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Depressivo Maior/genética , Feminino , Humanos , Inteligência/genética , Masculino , Transtornos Psicóticos/psicologia , Fatores de Risco , Análise e Desempenho de Tarefas , Adulto Jovem
Am J Med Genet B Neuropsychiatr Genet ; 159B(2): 192-200, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22213687


Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI and IPIP inventories) plus related mood states of anxiety and depression. Seventy single nucleotide polymorphisms (SNPs) in six brain expressed, longevity candidate genes (AFG3L2, FRAP1, MAT1A, MAT2A, SYNJ1, and SYNJ2) were typed in over 1,000 70-year old participants from the Lothian Birth Cohort of 1936 (LBC1936). No SNPs were associated with the personality and psychological distress traits at a Bonferroni corrected level of significance (P < 0.0002), but there was an over-representation of nominally significant (P < 0.05) SNPs in the synaptojanin-2 (SYNJ2) gene associated with agreeableness and symptoms of depression. Eight SNPs which showed nominally significant association across personality measurement instruments were tested in an extremely large replication sample of 17,106 participants. SNP rs350292, in SYNJ2, was significant: the minor allele was associated with an average decrease in NEO agreeableness scale scores of 0.25 points, and 0.67 points in the restricted analysis of elderly cohorts (most aged >60 years). Because we selected a specific set of longevity genes based on functional genomics findings, further research on other longevity gene candidates is warranted to discover whether they are relevant candidates for personality and psychological distress traits.

Marcadores Genéticos/genética , Longevidade/genética , Transtornos da Personalidade/genética , Transtornos da Personalidade/psicologia , Monoéster Fosfórico Hidrolases/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Transtornos de Ansiedade/genética , Estudos de Coortes , Depressão/genética , Feminino , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/diagnóstico , Testes de Personalidade , Fenótipo , Reação em Cadeia da Polimerase , Adulto Jovem