Trait anxiety affects the orofacial nociceptive response in rats

The aims of the present study were to assess the influence of: a) trait anxiety on orofacial pain; and b) orofacial pain on state anxiety. Forty-four rats were initially exposed to the free-exploratory paradigm for the evaluation of their anxiety profiles. In accordance to the parameter "Percentage of time in the novel side", the animals were considered as presenting high or low levels of trait anxiety when presenting values below the 1st quartile, or above the 3rd quartile, respectively. A week later, formalin-1.5% was injected into the upper lip of each animal. The behavioural nociceptive response, characterized by increased orofacial rubbing (OR), was quantified for 30 minutes, as follows: Total time OR (0-30 minutes: total pain), 1st phase OR (0-6 minutes: neurogenic pain), and 2nd phase OR (12-30 minutes: inflammatory pain). Immediately after this test, but still under the effect of formalin, the rats were submitted to the Elevated Plus-maze test (EPM). The results showed that the high trait anxiety individuals presented higher frequency of OR than the low trait anxiety ones, except during the neurogenic pain period. However, no correlation was found between OR frequency and levels of state anxiety presented on the EPM. In conclusion, the animals presenting higher anxiety profiles were the most susceptible to orofacial pain, nevertheless, orofacial pain did not influence state anxiety

Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.Support was provided by FAPESP-INCT - grant number: 2008/57899-7; FAPESP-CEPID - grant number: 2013/08028-1; CNPq [http://www.fapesp.br/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

CNVs at the chromosomal regions 15q13.3, 16p11.2 and 22q13 in the Brazilian individuals with ASD.

<p><b>Neurol. Dis.</b> - Neurological Disorder; “<b>–</b>” – not reported in the literature; “<b>+</b>” reported in the literature; del – deletion; dup – duplication; n.a. – not available; pat - paternal; mat - maternal;</p>¥<p>- ASD-affected individual 10 was described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107705#pone.0107705-Jehee1" target="_blank">[37]</a>; * CNVs at 15q13.3 and 15q11.2 are present in both parents;</p><p>CNVs at the chromosomal regions 15q13.3, 16p11.2 and 22q13 in the Brazilian individuals with ASD.</p

Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil

This work was supported by Decit, SCTIE, Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Científico - CNPq (440685/ 2016-8, 440856/2016-7 and 421598/2018-2), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES - (88887.130716/2016-00), European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement (734548), STARBIOS (709517), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ (E-26/2002.930/2016), International Development Research Centre (IDRC) Canada (108411-001), European Union’s Horizon 2020 under grant agreements ZIKACTION (734857) and ZIKAPLAN (734548).Fundação Ezequiel Dias. Laboratório Central de Saúde Pública do Estado de Minas Gerais. Belo Horizonte, MG, Brazil / Latin American Genomic Surveillance Arboviral Network.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil / Latin American Genomic Surveillance Arboviral Network.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil Latin American Genomic Surveillance Arboviral Network.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia. Manaus, AM, Brazil.Secretaria de Saúde do Estado de Mato Grosso do Sul. Laboratório Central de Saúde Pública. Campo Grande, MS, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública do Estado de Minas Gerais. Belo Horizonte, MG, Brazil.Laboratório Central de Saúde Pública Dr. Giovanni Cysneiros. Goiânia, GO, Brazil.Laboratório Central de Saúde Pública Professor Gonçalo Moniz. Salvador, BA, Brazil.Secretaria de Saúde do Estado da Bahia. Salvador, BA, Brazil.Laboratório Central de Saúde Pública Dr. Milton Bezerra Sobral. Recife, PE, Brazil.Laboratório Central de Saúde Pública do Estado de Mato Grosso. Cuiabá, MT, Brazil.Laboratório Central de Saúde Pública do Distrito Federal. Brasília, DF, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública do Estado de Minas Gerais. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Coordenação Geral dos Laboratórios de Saúde Pública. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Coordenação Geral dos Laboratórios de Saúde Pública. Brasília, DF, Brazil.Organização Pan-Americana da Saúde / Organização Mundial da Saúde. Brasília, DF, Brazil.Organização Pan-Americana da Saúde / Organização Mundial da Saúde. Brasília, DF, Brazil.Organização Pan-Americana da Saúde / Organização Mundial da Saúde. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde Coordenação Geral das Arboviroses. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde Coordenação Geral das Arboviroses. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde Coordenação Geral das Arboviroses. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde Coordenação Geral das Arboviroses. Brasília, DF, Brazil.Fundação Hemocentro de Ribeirão Preto. Ribeirão Preto, SP, Brazil.Gorgas Memorial Institute for Health Studies. Panama, Panama.Universidade Federal da Bahia. Vitória da Conquista, BA, Brazil.Laboratorio Central de Salud Pública. Asunción, Paraguay.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Coordenação Geral dos Laboratórios de Saúde Pública. Brasília, DF, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, BrazilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública do Estado de Mato Grosso do Sul. Campo Grande, MS, Brazil.Laboratório Central de Saúde Pública do Estado de Mato Grosso do Sul. Campo Grande, MS, Brazil.Instituto de Investigaciones en Ciencias de la Salud. San Lorenzo, Paraguay.Secretaria de Estado de Saúde de Mato Grosso do Sul. Campo Grande, MS, Brazil.Fundação Oswaldo Cruz. Campo Grande, MS, Brazil.Fundação Hemocentro de Ribeirão Preto. Ribeirão Preto, SP, Brazil.Laboratório Central de Saúde Pública Dr. Giovanni Cysneiros. Goiânia, GO, Brazil.Laboratório Central de Saúde Pública Dr. Giovanni Cysneiros. Goiânia, GO, Brazil.Laboratório Central de Saúde Pública Professor Gonçalo Moniz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública Dr. Milton Bezerra Sobral. Recife, PE, Brazil.Laboratório Central de Saúde Pública do Distrito Federal. Brasília, DF, Brazil.Secretaria de Saúde de Feira de Santana. Feira de Santana, Ba, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Secretaria de Saúde do Estado de Minas Gerais. Belo Horizonte, MG, Brazil.Hospital das Forças Armadas. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brazil.Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Lisboa, Portugal.University of Sydney. School of Life and Environmental Sciences and School of Medical Sciences. Marie Bashir Institute for Infectious Diseases and Biosecurity. Sydney, NSW, Australia.University of KwaZulu-Natal. College of Health Sciences. KwaZulu-Natal Research Innovation and Sequencing Platform. Durban, South Africa.University of Oxford. Peter Medawar Building. Department of Zoology. Oxford, UK.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Universidade Estadual de Feira de Santana. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brazil.Universidade de Brasília. Brasília, DF, Brazil.Universidade Salvador. Salvador, BA, Brazil.Fundação Ezequiel Dias. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hantaviroses e Rickettsioses. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia. Manaus, AM, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina Veterinária. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina Veterinária. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública do Estado do Paraná. Curitiba, PR, Brazil.Laboratório Central de Saúde Pública do Estado de Rondônia. Porto Velho, RO, Brazil.Laboratório Central de Saúde Pública do Estado do Amazonas. Manaus, AM, Brazil.Laboratório Central de Saúde Pública do Estado do Rio Grande do Norte. Natal, RN, Brazil.Laboratório Central de Saúde Pública do Estado de Mato Grosso. Cuiabá, MT, Brazil.Laboratório Central de Saúde Pública Professor Gonçalo Moniz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública Professor Gonçalo Moniz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Instituto Adolfo Lutz. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade de São Paulo. Instituto de Medicina Tropical. São Paulo, SP, Brazil.Universidade de São Paulo. Instituto de Medicina Tropical. São Paulo, SP, Brazil.Universidade de São Paulo. Instituto de Medicina Tropical. São Paulo, SP, Brazil.University of Oxford. Peter Medawar Building. Department of Zoology. Oxford, UK.Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui. Pergamino, Argentina.Gorgas Memorial Institute for Health Studies. Panama, Panama.Gorgas Memorial Institute for Health Studies. Panama, Panama.Gorgas Memorial Institute for Health Studies. Panama, Panama.Instituto de Salud Pública de Chile. Santiago, Chile.Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez. Ciudad de México, México.Instituto Nacional de Enfermedades Infecciosas Dr Carlos G Malbrán. Buenos Aires, Argentina.Ministerio de Salud Pública de Uruguay. Montevideo, Uruguay.Instituto Costarricense de Investigación y Enseñanza em Nutrición y Salud. Tres Ríos, Costa Rica.Instituto Nacional de Investigacion en Salud Publica Dr Leopoldo Izquieta Pérez. Guayaquil, Ecuador.Instituto Nacional de Investigacion en Salud Publica Dr Leopoldo Izquieta Pérez. Guayaquil, Ecuador.Universidade Federal de Pernambuco. Recife, PE, Brazil.Secretaria de Saúde do Estado de Minas Gerais. Belo Horizonte. MG, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasília, DF, Brazil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.Fundação Hemocentro de Ribeirão Preto. Ribeirão Preto, SP, Brazil.Secretaria de Saúde de Feira de Santana. Feira de Santana, BA, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015–2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses

Analysis of Shared Heritability in Common Disorders of the Brain

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology