American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

{"title":"Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith–Magenis-like syndrome","authors":"Francesca Cogliati,&nbsp;Letizia Straniero,&nbsp;Valeria Rimoldi,&nbsp;Maura Masciadri,&nbsp;Sara Perego,&nbsp;Berardo Rinaldi,&nbsp;Donatella Milani,&nbsp;Davide Gentilini,&nbsp;Lidia Larizza,&nbsp;Rosanna Asselta,&nbsp;Silvia Russo,&nbsp;Maria Francesca Bedeschi","doi":"10.1002/ajmg.b.32976","DOIUrl":"10.1002/ajmg.b.32976","url":null,"abstract":"<p>Loss-of-function <i>CHD2</i> (chromodomain helicase DNA-binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families. We detect the first case of parental gonosomal <i>CHD2</i> mosaicism disclosed by two brothers showing mild ID, born to healthy parents. The eldest brother has a history of drug-controlled generalized tonic–clonic seizures and displays sleep disorder and aggressive behavior suggestive of Smith–Magenis syndrome (SMS). Analysis of brothers’ DNAs by next-generation sequencing (NGS) custom gene panel for pediatric epilepsy and/or ID disclosed in both the same pathogenic <i>CHD2</i> variant. Additional NGS experiment on genomic DNA from parents’ peripheral blood and from buccal swab raised the suspicion of low-grade gonosomal mosaicism in the unaffected mother subsequently confirmed by digital polymerase chain reaction (dPCR). This report underlines as worthwhile <i>CHD2</i> screening in individuals presenting ID/developmental delay, with/without epilepsy, and behavior and sleep disorders suggestive of SMS. Detecting a <i>CHD2</i> variant should prime testing probands' parents by NGS coupled to dPCR on different tissues to exclude/confirm gonosomal mosaicism and define the recurrence risk.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Population features of alleles and genotypes frequency distribution of polymorphic genetic markers of antipsychotic medications pharmacokinetics in the Kazakh population","authors":"","doi":"10.1002/ajmg.b.32972","DOIUrl":"10.1002/ajmg.b.32972","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>Saduakassova, K. Z., &amp; Svyatova, G. S. (2022). Population features of alleles and genotypes frequency distribution of polymorphic genetic markers of antipsychotic medications pharmacokinetics in the Kazakh population. <i>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</i>, 189B: 100–107. https://doi.org/10.1002/ajmg.b.32893</p>\u0000 \u0000 <p>The above article published online on 16 May 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Editor, Stephen J. Glatt, and Wiley Periodicals, LLC. The retraction has been agreed following concerns raised by a third party regarding the peer review process. Further investigation by the publisher has found manipulation of the peer review process. As a result, the conclusions reported in the article are not considered reliable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disentangling differing relationships between internalizing disorders and alcohol use","authors":"Maizy S. Brasher,&nbsp;Andrew D. Grotzinger,&nbsp;Naomi P. Friedman,&nbsp;Harry R. Smolker,&nbsp;Luke M. Evans","doi":"10.1002/ajmg.b.32975","DOIUrl":"10.1002/ajmg.b.32975","url":null,"abstract":"<p>Both internalizing disorders and alcohol use have dramatic, wide-spread implications for global health. Previous work has established common phenotypic comorbidity among these disorders, as well as shared genetic variation underlying them both. We used genomic structural equation modeling to investigate the shared genetics of internalizing, externalizing, and alcohol use traits, as well as to explore whether specific domains of internalizing symptoms mediate the contrasting relationships with problematic alcohol use compared to alcohol consumption. We also examined patterns of genetic correlations between similar traits within additional Finnish and East Asian ancestry groups. When the shared genetic influence of externalizing psychopathology was accounted for, the genetic effect of internalizing traits on alcohol use was reduced, suggesting the important role of common genetic factors underlying multiple psychiatric disorders and their genetic influences on comorbidity of internalizing and alcohol use traits. Individual internalizing domains had contrasting effects on frequency of alcohol consumption, which demonstrate the complex system of pleiotropy that exists, even within similar disorders, and can be missed when evaluating only relationships among formal diagnoses. Future work must consider the broad effects of shared psychopathology along with the fine-scale effects of heterogeneity within disorders to more fully understand the biology underlying complex traits.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediational pathways between aggregate genetic liability and nonfatal suicide attempt: A Swedish population-based cohort","authors":"Séverine Lannoy,&nbsp;Henrik Ohlsson,&nbsp;Mallory Stephenson,&nbsp;Jan Sundquist,&nbsp;Kristina Sundquist,&nbsp;Alexis C. Edwards","doi":"10.1002/ajmg.b.32974","DOIUrl":"10.1002/ajmg.b.32974","url":null,"abstract":"<p>Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRS_SA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRS_SA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15–25 years (<i>N</i>_females = 850,278 and <i>N</i>_males = 899,366), 26–35 years (<i>N</i>_females = 800,189 and <i>N</i>_males = 861,774), and 36–45 years (<i>N</i>_females = 498,285 and <i>N</i>_males = 535,831). The association between FGRS_SA and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15–25 years, HR_total = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25–36 years, HR_total = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25–36 years) in females (HR_total = 1.46 [1.44; 1.49], mediation = 7%) and males (HR_total = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRS_SA was higher at ages of 15–25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139745867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and molecular mechanisms of the early growth response 3 gene in schizophrenia","authors":"Qi He,&nbsp;Ruochun Li,&nbsp;Nannan Zhong,&nbsp;Jie Ma,&nbsp;Fayi Nie,&nbsp;Rui Zhang","doi":"10.1002/ajmg.b.32969","DOIUrl":"10.1002/ajmg.b.32969","url":null,"abstract":"<p>Schizophrenia is a chronic, debilitating mental illness caused by both genetic and environmental factors. Genetic factors play a major role in schizophrenia development. Early growth response 3 (EGR3) is a member of the EGR family, which is associated with schizophrenia. Accumulating studies have investigated the relationship between EGR3 and schizophrenia. However, the role of EGR3 in schizophrenia pathogenesis remains unclear. In the present review, we focus on the progress of research related to the role of EGR3 in schizophrenia, including association studies between <i>EGR3</i> and schizophrenia, abnormal gene expressional analysis of <i>EGR3</i> in schizophrenia, biological function studies of EGR3 in schizophrenia, the molecular regulatory mechanism of EGR3 and schizophrenia susceptibility candidate genes, and possible role of EGR3 in the immune system function in schizophrenia. In summary, EGR3 is a schizophrenia risk candidate factor and has comprehensive regulatory roles in schizophrenia pathogenesis. Further studies investigating the molecular mechanisms of EGR3 in schizophrenia are warranted for understanding the pathophysiology of this disorder as well as the development of new therapeutic strategies for the treatment and control of this disorder.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Family-based genetic analysis in schizophrenia by whole-exome sequence to identify rare pathogenic variants","authors":"Binli Shang,&nbsp;Runxu Yang,&nbsp;Kun Lian,&nbsp;Lei Dong,&nbsp;Hongbing Liu,&nbsp;Tianlan Wang,&nbsp;Guangya Yang,&nbsp;Kang Xi,&nbsp;Xiufeng Xu,&nbsp;Yuqi Cheng","doi":"10.1002/ajmg.b.32968","DOIUrl":"10.1002/ajmg.b.32968","url":null,"abstract":"<p>Schizophrenia (SCZ) is influenced by a combination of genetic and environmental factors. Although several studies have been conducted to identify the causative loci and genes, few of these loci or genes can be repeated due to the high phenotypic and genetic heterogeneity of disease, and their mechanisms are not fully understood. There may be some “missing heritability” that has not yet been found. In order to investigate the deleterious heritable mutations, whole-exome sequencing (WES) in pedigrees with SCZ was used in the current work. Two unrelated pedigrees with SCZ were recruited to perform WES. Genetic analysis was next performed to find potential variants in accordance with the prioritized strategy. Followed by genetic analysis to detect candidate variants according to the prioritized strategy. Next, a series of algorithms was used to predict the pathogenicity of variants. Sanger sequencing was finally conducted to verify the co-segregation. Recessive mutations in six genes (<i>TFEB, SNAI2, TFAP2B, PRKDC, ST18</i> in Pedigree 1 and <i>PKHD1L1</i> in Pedigree 2) that co-segregated with SCZ in two families were discovered through genetic analysis by WES. Sanger sequencing verified that all of the mutations in the affected siblings were homozygous. These results corroborated the hypothesis that SCZ exhibits strong heterogeneity and complex inheritance patterns. The newly discovered homozygous variations deepen our understanding of the mutation spectrum and offer more proof for the involvement of <i>TFEB, SNAI2, TFAP2B, PRKDC, ST18,</i> and <i>PKHD1L1</i> in the development of SCZ.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruno Schulz's 1930 article “The Hereditary Relationships of Old-Age Paranoid Psychosis”","authors":"Kenneth S. Kendler,&nbsp;Astrid Klee","doi":"10.1002/ajmg.b.32965","DOIUrl":"10.1002/ajmg.b.32965","url":null,"abstract":"<p>In the 1899 6th edition of his influential textbook, Kraepelin proposed a diagnostic category of “Old-Age Paranoid Psychosis.” In this 1930 article, Bruno Schulz studied the morbid risk (MR) of several disorders and traits in the parents, siblings, offspring, and nieces/nephews of 51 probands with “Old-Age Paranoid Psychosis.” His results permitted an evaluation of the validity of Kraepelin's category of Old-Age Paranoid Psychosis, in particular, whether it was a form of psychosis resulting from “senile changes” or late-onset schizophrenia. The MR of schizophrenia in these four groups of relatives varied from 0 to 2.4% with 3 of 4 somewhat higher than population expectations but much lower than parallel results in relatives of schizophrenics. By contrast, the rates of eccentricity in these relatives were uniformly elevated over population rates, sometimes approaching those seen in relatives of schizophrenics. Schulz concluded, from his study, that Old-Age Paranoid Psychosis was a distinct disorder not closely related to schizophrenia. However, he suggested that a family history and/or a premorbid trait of eccentricity increases the risk of developing a paranoid psychosis in old age, particularly when associated with physical or mental decline. He was uncertain about whether the trait of eccentricity he found in this study was very similar or distinct from that observed in excess in relatives of schizophrenics. This study was the first, to the best of our knowledge, to use a family study design explicitly to address a nosologic question—in this case the familial relationship between Old-Age Paranoid Psychosis and schizophrenia.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel genome-wide associations for effort valuation and psychopathology in children and adults","authors":"Nicholas H. Nguyen,&nbsp;T. Mitchell Mazza,&nbsp;Jonathan L. Hess,&nbsp;Avery B. Albert,&nbsp;Sarah Elfstrom,&nbsp;Patricia Forken,&nbsp;Steven D. Blatt,&nbsp;Wanda P. Fremont,&nbsp;Stephen V. Faraone,&nbsp;Stephen J. Glatt","doi":"10.1002/ajmg.b.32964","DOIUrl":"10.1002/ajmg.b.32964","url":null,"abstract":"<p>The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the “Positive Valence Systems” domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of “effort” and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6–12 and their parents (<i>n</i> = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses “effort” according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in <i>MAGMA</i>, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene-set enrichment analysis yielded significant associations between “effort” and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish “effort” as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting ADHD in alcohol dependence using polygenic risk scores for ADHD","authors":"Kejal H. S. Patel,&nbsp;G. Bragi Walters,&nbsp;Hreinn Stefánsson,&nbsp;Kári Stefánsson,&nbsp;Franziska Degenhardt,&nbsp;Markus Nothen,&nbsp;Tracey Van Der Veen,&nbsp;Ditte Demontis,&nbsp;Anders Borglum,&nbsp;Mark Kristiansen,&nbsp;Nicholas J. Bass,&nbsp;Andrew McQuillin","doi":"10.1002/ajmg.b.32967","DOIUrl":"10.1002/ajmg.b.32967","url":null,"abstract":"<p>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a high degree of comorbidity, including substance misuse. We aimed to assess whether ADHD polygenic risk scores (PRS) could predict ADHD diagnosis in alcohol dependence (AD). ADHD PRS were generated for 1223 AD subjects with ADHD diagnosis information and 1818 healthy controls. ADHD PRS distributions were compared to evaluate the differences between healthy controls and AD cases with and without ADHD. We found increased ADHD PRS means in the AD cohort with ADHD (mean 0.30, standard deviation (SD) 0.92; <i>p</i> = 3.9 × 10⁻⁶); and without ADHD (mean − 0.00, SD 1.00; <i>p</i> = 5.2 × 10⁻⁵) compared to the healthy control subjects (mean − 0.17, SD 0.99). The ADHD PRS means differed within the AD group with a higher ADHD PRS mean in those with ADHD, odds ratio (OR) 1.34, confidence interval (CI) 1.10 to 1.65; <i>p</i> = 0.002. This study showed a positive relationship between ADHD PRS and risk of ADHD in individuals with co-occurring AD indicating that ADHD PRS may have utility in identifying individuals that are at a higher or lower risk of ADHD. Further larger studies need to be conducted to confirm the reliability of the results before ADHD PRS can be considered as a robust biomarker for diagnosis.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol","authors":"James J. Crowley,&nbsp;Carolina Cappi,&nbsp;Marcos E. Ochoa-Panaifo,&nbsp;Renee M. Frederick,&nbsp;Minjee Kook,&nbsp;Andrew D. Wiese,&nbsp;Diana Rancourt,&nbsp;Elizabeth G. Atkinson,&nbsp;Paola Giusti-Rodriguez,&nbsp;Jacey L. Anderberg,&nbsp;Latin American Trans-ancestry INitiative for OCD genomics,&nbsp;Brazilian Obsessive-Compulsive Spectrum Disorder Working Group,&nbsp;Jonathan S. Abramowitz,&nbsp;Victor R. Adorno,&nbsp;Cinthia Aguirre,&nbsp;Gilberto S. Alves,&nbsp;Gustavo S. Alves,&nbsp;NaEshia Ancalade,&nbsp;Alejandro A. Arellano Espinosa,&nbsp;Paul D. Arnold,&nbsp;Daphne M. Ayton,&nbsp;Izabela G. Barbosa,&nbsp;Laura Marcela Barón Castano,&nbsp;Cynthia N. Barrera,&nbsp;María Celeste Berardo,&nbsp;Dayan Berrones,&nbsp;John R. Best,&nbsp;Tim B. Bigdeli,&nbsp;Christie L. Burton,&nbsp;Joseph D. Buxbaum,&nbsp;Jennifer L. Callahan,&nbsp;Maria Cecília B. Carneiro,&nbsp;Sandra L. Cepeda,&nbsp;Evelyn Chazelle,&nbsp;Jessica M. Chire,&nbsp;Macarena Churruca Munoz,&nbsp;Pamela Claisse Quiroz,&nbsp;Journa Cobite,&nbsp;Jonathan S. Comer,&nbsp;Daniel L. Costa,&nbsp;Jennifer Crosbie,&nbsp;Victor O. Cruz,&nbsp;Guillermo Dager,&nbsp;Luisa F. Daza,&nbsp;Anabel de la Rosa-Gómez,&nbsp;Daniela del Río,&nbsp;Fernanda Z. Delage,&nbsp;Carolina B. Dreher,&nbsp;Lucila Fay,&nbsp;Tomas Fazio,&nbsp;Ygor A. Ferrão,&nbsp;Gabriela M. Ferreira,&nbsp;Edith G. Figueroa,&nbsp;Leonardo F. Fontenelle,&nbsp;Diego A. Forero,&nbsp;Daniele T. H. Fragoso,&nbsp;Bharathi S. Gadad,&nbsp;Sheldon R. Garrison,&nbsp;Andres González,&nbsp;Laura D. Gonzalez,&nbsp;Marco A. González,&nbsp;Polaris Gonzalez-Barrios,&nbsp;Wayne K. Goodman,&nbsp;Dorothy E. Grice,&nbsp;Jerry Guintivano,&nbsp;Daniel G. Guttfreund,&nbsp;Andrew G. Guzick,&nbsp;Matthew W. Halvorsen,&nbsp;Joseph D. Hovey,&nbsp;Hailiang Huang,&nbsp;Jonathan Irreño-Sotomonte,&nbsp;Reinhard Janssen-Aguilar,&nbsp;Matias Jensen,&nbsp;Alexandra Z. Jimenez Reynolds,&nbsp;Joali Alexandra Juárez Lujambio,&nbsp;Nasim Khalfe,&nbsp;Madison A. Knutsen,&nbsp;Caleb Lack,&nbsp;Nuria Lanzagorta,&nbsp;Monicke O. Lima,&nbsp;Melanie O. Longhurst,&nbsp;David A. Lozada Martinez,&nbsp;Elba S. Luna,&nbsp;Andrea H. Marques,&nbsp;Molly S. Martinez,&nbsp;Maria de Los Angeles Matos,&nbsp;Caitlyn E. Maye,&nbsp;Joseph F. McGuire,&nbsp;Gabriela Menezes,&nbsp;Charlene Minaya,&nbsp;Tomás Miño,&nbsp;Sara M. Mithani,&nbsp;Circe Montes de Oca,&nbsp;Alonso Morales-Rivero,&nbsp;Maria E. Moreira-de-Oliveira,&nbsp;Olivia J. Morris,&nbsp;Sandra I. Muñoz,&nbsp;Zainab Naqqash,&nbsp;Ambar A. Núñez Bracho,&nbsp;Belinda E. Núñez Bracho,&nbsp;Maria Corina Ochoa Rojas,&nbsp;Luis A. Olavarria Castaman,&nbsp;Trinidad Olivos Balmaceda,&nbsp;Iliana Ortega,&nbsp;Darpan I. Patel,&nbsp;Ainsley K. Patrick,&nbsp;Mariel Paz y Mino,&nbsp;Jose L. Perales Orellana,&nbsp;Bárbara Perdigão Stumpf,&nbsp;Tamara Peregrina,&nbsp;Tania Pérez Duarte,&nbsp;Kelly L. Piacsek,&nbsp;Maritza Placencia,&nbsp;María Belén Prieto,&nbsp;Lucas C. Quarantini,&nbsp;Yana Quarantini-Alvim,&nbsp;Renato T. Ramos,&nbsp;Iaroslava C. Ramos,&nbsp;Vanessa R. Ramos,&nbsp;Kesley A. Ramsey,&nbsp;Elise V. Ray,&nbsp;Margaret A. Richter,&nbsp;Bradley C. Riemann,&nbsp;Juan C. Rivas,&nbsp;Maria C. Rosario,&nbsp;Camilo J. Ruggero,&nbsp;Angel A. Ruiz-Chow,&nbsp;Alejandra Ruiz-Velasco,&nbsp;Melisa N. Sagarnaga,&nbsp;Aline S. Sampaio,&nbsp;Leonardo C. Saraiva,&nbsp;Russell J. Schachar,&nbsp;Sophie C. Schneider,&nbsp;Ethan J. Schweissing,&nbsp;Laura D. Seligman,&nbsp;Roseli G. Shavitt,&nbsp;Keaton J. Soileau,&nbsp;S. Evelyn Stewart,&nbsp;Shaina B. Storch,&nbsp;Emily R. Strouphauer,&nbsp;Vissente Tapia Cuevas,&nbsp;Kiara R. Timpano,&nbsp;Beatriz Treviño-de la Garza,&nbsp;Alexie Vallejo-Silva,&nbsp;Javier Vargas-Medrano,&nbsp;María I. Vásquez,&nbsp;Guadalupe Vidal Martinez,&nbsp;Saira A. Weinzimmer,&nbsp;Mauricio A. Yanez,&nbsp;Gwyneth Zai,&nbsp;Lina M. Zapata-Restrepo,&nbsp;Luz M. Zappa,&nbsp;Raquel M. Zepeda-Burgos,&nbsp;Anthony W. Zoghbi,&nbsp;Euripedes C. Miguel,&nbsp;Carolyn I. Rodriguez,&nbsp;Mayra C. Martinez Mallen,&nbsp;Pablo R. Moya,&nbsp;Tania Borda,&nbsp;María Beatriz Moyano,&nbsp;Manuel Mattheisen,&nbsp;Stacey Pereira,&nbsp;Gabriel Lázaro-Muñoz,&nbsp;Karen G. Martinez-Gonzalez,&nbsp;Michele T. Pato,&nbsp;Humberto Nicolini,&nbsp;Eric A. Storch","doi":"10.1002/ajmg.b.32962","DOIUrl":"10.1002/ajmg.b.32962","url":null,"abstract":"<p>Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but &gt;95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}