Michele T Pato

University of Southern California, Los Ángeles, California, United States

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Publications (114)795.93 Total impact

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    ABSTRACT: Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis, droplet digital PCR and genome mapping, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ∼3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI, yet found no association.
    Nature Genetics 06/2015; DOI:10.1038/ng.3340 · 29.65 Impact Factor
  • 04/2015; 13(2):142-147. DOI:10.1176/appi.focus.130208
  • European Psychiatry 03/2015; 30:349. DOI:10.1016/S0924-9338(15)30274-1 · 3.21 Impact Factor
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    Molecular Psychiatry 02/2015; 20(2):207-214. DOI:10.1038/mp.2013.195 · 15.15 Impact Factor
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    ABSTRACT: Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 01/2015; DOI:10.1016/j.ajhg.2014.12.006 · 10.99 Impact Factor
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    ABSTRACT: To examine the psychometric properties of the Brazilian Portuguese version of the Family Accommodation Scale for Obsessive-Compulsive Disorder – Interviewer-Rated (FAS-IR).MethodA total of 114 family members of patients with obsessive-compulsive disorder (OCD) were assessed. The following analyses of the FAS-IR were carried out: internal consistency, inter-rater and test-retest reliability, and exploratory factor analysis.ResultsThe Brazilian Portuguese version of the FAS-IR showed excellent inter-rater reliability (intraclass correlation coefficient [ICC] = 0.94) and acceptable test-retest reliability (ICC = 0.77), with no significant differences in FAS-IR scores. Factor analysis produced three factors for the scale. However, factor loadings were not well defined within each factor, and the factors did not have distinct constructs. Thus, a global analysis approach was chosen, revealing good internal consistency of the scale as a whole (Cronbach’s α = 0.805).Conclusions The Brazilian Portuguese FAS-IR showed sound psychometric properties for the evaluation of family accommodation, and is, therefore, a reliable instrument for use in research and clinical practice.
    Comprehensive Psychiatry 11/2014; 57. DOI:10.1016/j.comppsych.2014.11.017 · 2.26 Impact Factor
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    ABSTRACT: Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and MIR2682 (miR2682), two microRNA genes important for neuronal function. We sequenced ∼6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 × 10(-4)). We further identified its risk allele T in 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 11/2014; 95(6). DOI:10.1016/j.ajhg.2014.11.001 · 10.99 Impact Factor
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    ABSTRACT: Objective: The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes. Method: In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies. Results: The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%). Conclusions: Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.
    American Journal of Psychiatry 09/2014; DOI:10.1176/appi.ajp.2014.14040435 · 13.56 Impact Factor
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    ABSTRACT: Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10-4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
    American Journal of Psychiatry 08/2014; 172(1). DOI:10.1176/appi.ajp.2014.13101306 · 13.56 Impact Factor
  • Sarah M Hartz, Laura J Bierut, Michele T Pato
    JAMA Psychiatry 08/2014; 71(8):969. DOI:10.1001/jamapsychiatry.2014.707 · 12.01 Impact Factor
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    ABSTRACT: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
    Nature 07/2014; 511(7510):421-427. DOI:10.1038/nature13595 · 42.35 Impact Factor
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    ABSTRACT: Objectives Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
    Journal of the American Academy of Child and Adolescent Psychiatry 06/2014; 53(8):910-919. DOI:10.1016/j.jaac.2014.04.022 · 6.35 Impact Factor
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    ABSTRACT: IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.
    JAMA Psychiatry 05/2014; DOI:10.1001/jamapsychiatry.2014.528 · 12.01 Impact Factor
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    ABSTRACT: Importance Although early mortality in severe psychiatric illness is linked to smoking and alcohol, to our knowledge, no studies have comprehensively characterized substance use behavior in severe psychotic illness. In particular, recent assessments of substance use in individuals with mental illness are based on population surveys that do not include individuals with severe psychotic illness.Objective To compare substance use in individuals with severe psychotic illness with substance use in the general population.Design, Setting, and Participants We assessed comorbidity between substance use and severe psychotic disorders in the Genomic Psychiatry Cohort. The Genomic Psychiatry Cohort is a clinically assessed, multiethnic sample consisting of 9142 individuals with the diagnosis of schizophrenia, bipolar disorder with psychotic features, or schizoaffective disorder, and 10 195 population control individuals.Main Outcomes and Measures Smoking (smoked >100 cigarettes in a lifetime), heavy alcohol use (>4 drinks/day), heavy marijuana use (>21 times of marijuana use/year), and recreational drug use.Results Relative to the general population, individuals with severe psychotic disorders have increased risks for smoking (odds ratio, 4.6; 95% CI, 4.3-4.9), heavy alcohol use (odds ratio, 4.0; 95% CI, 3.6-4.4), heavy marijuana use (odds ratio, 3.5; 95% CI, 3.2-3.7), and recreational drug use (odds ratio, 4.6; 95% CI, 4.3-5.0). All races/ethnicities (African American, Asian, European American, and Hispanic) and both sexes have greatly elevated risks for smoking and alcohol, marijuana, and drug use. Of specific concern, recent public health efforts that have successfully decreased smoking among individuals younger than age 30 years appear to have been ineffective among individuals with severe psychotic illness (interaction effect between age and severe mental illness on smoking initiation, P = 4.5 × 105).Conclusions and Relevance In the largest assessment of substance use among individuals with severe psychotic illness to date, we found the odds of smoking and alcohol and other substance use to be dramatically higher than recent estimates of substance use in mild mental illness.
    03/2014; 71(3):248. DOI:10.1001/jamapsychiatry.2013.3726
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    ABSTRACT: Obsessive-compulsive disorder (OCD) impacts family functioning as family members modify their personal and family routines, participate in rituals, and provide reassurance. These behaviors have been identified as family accommodation (FA), a phenomenon that, if ignored, may facilitate OCD symptoms and lead to poorer prognosis. Because FA has been recognized as a predictor of treatment outcome, we examined the prevalence of FA and identified patient and family socio-demographic and clinical variables associated with FA in an outpatient sample. The study comprised 228 subjects, namely, 114 patients with OCD and 114 family members, assessed before the patients entered a 12-session cognitive-behavioral group therapy program. A multivariate linear regression model was used to control for confounding factors and to evaluate variables independently associated with FA. FA was evaluated using the Family Accommodation Scale for Obsessive-Compulsive Disorder - Interviewer Rated (FAS-IR). FA was found to be highly prevalent among family members. Two patient factors positively associated with FA were OCD severity as measured by the Clinical Global Impressions Scale (CGI) and higher scores on the Obsessions dimension of the Obsessive-Compulsive Inventory - Revised (OCI-R). Family members' characteristics positively associated with FA were higher scores on the OCI-R hoarding subscale and being the patient's spouse. Our findings suggest that the early identification of patients and family members who could benefit from interventions aimed at reducing FA could improve treatment outcomes.
    Psychiatry and Clinical Neurosciences 02/2014; 68(8). DOI:10.1111/pcn.12172 · 1.62 Impact Factor
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    ABSTRACT: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single-marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene-wide significance were obtained by permutation (via 100,000 gene-dropping simulations) of Fisher's combined test of P-values for each locus. No single variant yielded significant experiment-wide evidence of association, for either the combined sample or in each subsample. Our gene-dropping simulations identified nominally significant gene-wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested. Using a gene-based approach to family-based association, we identified gene-wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs. © 2013 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2013; 162(8). DOI:10.1002/ajmg.b.32200 · 3.27 Impact Factor
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    ABSTRACT: A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5–3.0 Mb) at 22q11.2—the reciprocal of the well-known, risk-inducing deletion of this locus—are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.
    Molecular Psychiatry 11/2013; 19(1):37-40. DOI:10.1038/mp.2013.156 · 15.15 Impact Factor
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    ABSTRACT: Sleep PostersSESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PMPURPOSE: Insomnia is highly prevalent amongst patients with mental illness and has been implicated as both a risk factor and marker of disease severity in various psychiatric diseases, including schizophrenia. Recent studies have delineated distinct subtypes of insomnia based on overall sleep duration, with the "short sleep duration" variant associated with increased risk of cardiovascular diseases such as hypertension, coronary heart disease and stroke in a community-based cohort. However, no previous study has examined this relationship in schizophrenic patients. We evaluated the association between short sleep duration insomnia and select cardiovascular diseases in schizophrenics.METHODS: A total of 2,152 participants enrolled in the multi-center Genomic Psychiatric Cohort (GPC) self-reported their baseline sleep duration and medical comorbidities. In participants with schizophrenia or schizoaffective-depressed disorder, 1417 had symptoms of insomnia (mean age 42.4 years, 62% male, 55% non-white). This group was further stratified into "short sleep duration" insomnia, defined as sleep time ≤ six hours per night (n = 316) and normal sleep duration insomnia, defined as sleep time seven to nine hours per night, (n=989). Participates who reported greater than nine hours of sleep (n=112) were not included here. Chi square analysis was performed.RESULTS: Of the 1417 patients with insomnia, those with short sleep duration insomnia self-reported significantly more coronary heart disease (n=44, OR 1.58; 95% CI 1.09-2.31; p <0.05), hypertension (n=127, OR 1.42; 95% CI 1.10-1.84; p < 0.05) and stroke (n=26, OR 2.54; 95% CI 1.54-4.33; p <0.05) when compared to those who self-reported a normal sleep duration.CONCLUSIONS: Schizophrenics who self-reported insomnia symptoms and short sleep duration may have increased incidence of cardiovascular diseases such as hypertension, coronary heart disease and stroke. Further study to examine the strength of the association and possible confounders is warranted.CLINICAL IMPLICATIONS: Short sleep duration insomnia may be a distinct and modifiable risk factor for cardiovascular diseases such as hypertension, coronary heart disease and stroke in schizophrenics.DISCLOSURE: The following authors have nothing to disclose: Terese Hammond, Joleen Aguon, Janet Sobell, Brooke Sklar, Michele PatoNo Product/Research Disclosure Information.
    Chest 10/2013; 144(4_MeetingAbstracts):996A. DOI:10.1378/chest.1703315 · 7.13 Impact Factor
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    ABSTRACT: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
    PLoS Genetics 10/2013; 9(10):e1003864. DOI:10.1371/journal.pgen.1003864 · 8.17 Impact Factor
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    ABSTRACT: To investigate the extent to which the proportion of schizophrenia's additive genetic variation tagged by SNPs is shared by populations of European and African descent, we analyzed the largest combined African descent (AD [n = 2,142]) and European descent (ED [n = 4,990]) schizophrenia case-control genome-wide association study (GWAS) data set available, the Molecular Genetics of Schizophrenia (MGS) data set. We show how a method that uses genomic similarities at measured SNPs to estimate the additive genetic correlation (SNP correlation [SNP-rg]) between traits can be extended to estimate SNP-rg for the same trait between ethnicities. We estimated SNP-rg for schizophrenia between the MGS ED and MGS AD samples to be 0.66 (SE = 0.23), which is significantly different from 0 (p(SNP-rg = 0) = 0.0003), but not 1 (p(SNP-rg = 1) = 0.26). We re-estimated SNP-rg between an independent ED data set (n = 6,665) and the MGS AD sample to be 0.61 (SE = 0.21, p(SNP-rg = 0) = 0.0003, p(SNP-rg = 1) = 0.16). These results suggest that many schizophrenia risk alleles are shared across ethnic groups and predate African-European divergence.
    The American Journal of Human Genetics 08/2013; DOI:10.1016/j.ajhg.2013.07.007 · 10.99 Impact Factor

Publication Stats

5k Citations
795.93 Total Impact Points

Institutions

  • 2009–2015
    • University of Southern California
      • • Department of Psychiatry and Behavioral Sciences
      • • Keck School of Medicine
      Los Ángeles, California, United States
  • 2014
    • Keck School of Medicine USC
      Los Ángeles, California, United States
  • 2012–2014
    • University of California, Los Angeles
      • Department of Psychiatry and Biobehavioural Sciences
      Los Ángeles, California, United States
  • 2007
    • University at Albany, The State University of New York
      New York City, New York, United States
  • 2003–2007
    • State University of New York Upstate Medical University
      Syracuse, New York, United States
  • 2000–2006
    • University at Buffalo, The State University of New York
      • Department of Psychiatry
      Buffalo, NY, United States
  • 2005
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 2004
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
    • Center for Molecular Genetics
      Gif, Île-de-France, France
  • 2003–2004
    • University of Toronto
      • Department of Psychiatry
      Toronto, Ontario, Canada
  • 2001–2004
    • University of Coimbra
      • Faculdade de Medicina
      Coimbra, Distrito de Coimbra, Portugal
  • 1995
    • Rhode Island Hospital
      Providence, Rhode Island, United States
  • 1993
    • Brown University
      • Department of Psychiatry and Human Behavior
      Providence, RI, United States