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

{"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}

{"title":"Bruno Schulz's 1936 book “Methodology of medical genetic research particularly with regard to psychiatry”","authors":"Kenneth S. Kendler,&nbsp;Astrid Klee","doi":"10.1002/ajmg.b.32963","DOIUrl":"10.1002/ajmg.b.32963","url":null,"abstract":"<p>In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk. For the field work, Schulz emphasizes the importance of trust-building, confidentiality, collateral informants, and the use of medical and other administrative records, all ideally stored in personal files. Several methods of age-correction are reviewed. Schulz provides detailed algebraic treatments of these and other problems, including tests for etiologic homogeneity, with worked examples. He emphasizes two fundamental concerns in psychiatric genetics research: (i) its inter-dependency with the optimal diagnostic boundaries, which are rarely known and (ii) the genetic homogeneity of clinical samples. Given these problems, he is pessimistic about finding Mendelian transmission patterns. He assesses the predominant 19th-century method of psychiatric genetic investigation—“hereditary burden”—to be crude and biased by family size. Although written at a time of consolidation of Nazi power in Germany, this book nowhere endorses their racial/eugenic policies and can be seen as subtly questioning them.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477188","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":"Association of BDNF risk variant and dorsolateral cortical thickness with long-term treatment response to valproate in type I bipolar disorder: An exploratory study","authors":"Alejandra Monserrat Rodríguez-Ramírez,&nbsp;Valente Cedillo-Ríos,&nbsp;Marco Antonio Sanabrais-Jiménez,&nbsp;Claudia Becerra-Palars,&nbsp;Sandra Hernández-Muñoz,&nbsp;Hiram Ortega-Ortíz,&nbsp;Beatriz Camarena-Medellin","doi":"10.1002/ajmg.b.32966","DOIUrl":"10.1002/ajmg.b.32966","url":null,"abstract":"<p>Valproate is among the most prescribed drugs for bipolar disorder; however, 87% of patients do not report full long-term treatment response (LTTR) to this medication. One of valproate's suggested mechanisms of action involves the brain-derived neurotrophic factor (<i>BDNF</i>), expressed in the brain areas regulating emotions, such as the prefrontal cortex. Nonetheless, data about the role of <i>BDNF</i> in LTTR and its implications in the structure of the dorsolateral prefrontal cortex (dlPFC) is scarce. We explore the association of <i>BDNF</i> variants and dorsolateral cortical thickness (CT) with LTTR to valproate in bipolar disorder type I (BDI). Twenty-eight BDI patients were genotyped for <i>BDNF</i> polymorphisms rs1519480, rs6265, and rs7124442, and T1-weighted 3D brain scans were acquired. LTTR to valproate was evaluated with Alda's scale. A logistic regression analysis was conducted to evaluate LTTR according to <i>BDNF</i> genotypes and CT. We evaluated CT differences by genotypes with analysis of covariance. LTTR was associated with <i>BDNF</i> rs1519480 and right dlPFC thickness. Insufficient responders with the CC genotype had thicker right dlPFC than TC and TT genotypes. Full responders reported thicker right dlPFC in TC and TT genotypes. In conclusion, different patterns of CT related to <i>BDNF</i> genotypes were identified, suggesting a potential biomarker of LTTR to valproate in our population.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419820","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":"Systematic exploration of a decade of publications on psychiatric genetics in Latin America","authors":"Diana Garro-Núñez,&nbsp;María Jesús Picado-Martínez,&nbsp;Erika Espinoza-Campos,&nbsp;Daniela Ugalde-Araya,&nbsp;Gabriel Macaya,&nbsp;Henriette Raventós,&nbsp;Gabriela Chavarría-Soley","doi":"10.1002/ajmg.b.32960","DOIUrl":"10.1002/ajmg.b.32960","url":null,"abstract":"<p>Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene–environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673346","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":"William Boven's 1915 thesis “Similarity and Mendelism in the heredity of dementia praecox and manic-depressive insanity”","authors":"Kenneth S. Kendler,&nbsp;Virginia Justis","doi":"10.1002/ajmg.b.32961","DOIUrl":"10.1002/ajmg.b.32961","url":null,"abstract":"<p>Boven published, in 1915, his MD thesis at the University of Lausanne in which he examined 60 3- to 4-generation pedigrees ascertained from admitted patients with dementia praecox (DP) and manic-depressive insanity (MDI). He asked three questions: (i) were DP and MDI hereditary? (ii) were they the same or distinct conditions? and (iii) were they Mendelian disorders? Based on the rarity of environmental precipitants severe enough to cause disorder onset and the pattern of disorders in relatives, Boven concluded that both disorders were inherited. He found that MDI largely ran in families through direct transmission across generations while DP was only common in collateral relatives. Both pedigrees contained a substantial number of “psychopathic” (personality disordered) relatives in which DP and MDI pedigrees typically had, respectively, paranoid, and dysthymic/cyclothymic features. Boven concludes that their inheritance is largely distinct but not exclusive, as some pedigrees contained cases of both disorders. With assistance from Wilhelm Weinberg, Boven applied algebraic models with proband correction to rates of DP and MDI in sibships and found the results inconsistent with Mendelian transmission. His study represents among the first examinations, using “modern” methods, of the familial relationship between DP and MDI and the first published in French.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32961","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673347","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":"Influence of gut microbiota on the development of most prevalent neurodegenerative dementias and the potential effect of probiotics in elderly: A scoping review","authors":"David Mateo,&nbsp;Montse Marquès,&nbsp;José L. Domingo,&nbsp;Margarita Torrente","doi":"10.1002/ajmg.b.32959","DOIUrl":"10.1002/ajmg.b.32959","url":null,"abstract":"<p>Dementia is one of today's greatest public health challenges. Its high socio-economic impact and difficulties in diagnosis and treatment are of increasing concern to an aging world population. In recent years, the study of the relationship between gut microbiota and different neurocognitive disorders has gained a considerable interest. Several studies have reported associations between gut microbiota dysbiosis and some types of dementia. Probiotics have been suggested to restore dysbiosis and to improve neurocognitive symptomatology in these dementias. Based on these previous findings, the available scientific evidence on the gut microbiota in humans affected by the most prevalent dementias, as well as the probiotic trials conducted in these patients in recent years, have been here reviewed. Decreased concentrations of short-chain fatty acids (SCFA) and other bacterial metabolites appear to play a major role in the onset of neurocognitive symptoms in Alzheimer disease (AD) and Parkinson disease dementia (PDD). Increased abundance of proinflammatory taxa could be closely related to the more severe clinical symptoms in both, as well as in Lewy Bodies dementia. Important lack of information was noted in Frontotemporal dementia behavioral variant. Moreover, geographical differences in the composition of the gut microbiota have been reported in AD. Some potential beneficial effects of probiotics in AD and PDD have been reported. However, due to the controversial results further investigations are clearly necessary.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32959","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231767","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":"Psychiatric and neurological manifestations in adults with Smith–Magenis syndrome: A scoping review","authors":"Dorinde Korteling,&nbsp;Jiska L. I. Musch,&nbsp;Janneke R. Zinkstok,&nbsp;Erik Boot","doi":"10.1002/ajmg.b.32956","DOIUrl":"10.1002/ajmg.b.32956","url":null,"abstract":"<p>Smith–Magenis syndrome (SMS) is a neurodevelopmental disorder caused by a 17p11.2 deletion or a pathogenic variant of the RAI1 gene, which lies within the 17p11.2 region. Various psychiatric and neurological disorders have been reported in SMS, with most literature focusing on children and adolescents. To provide an overview of the current knowledge on this topic in adults with SMS, we performed a comprehensive scoping review of the relevant literature. Our findings suggest that many manifestations that are common in childhood persist into adulthood. Neuropsychiatric manifestations in adults with SMS include intellectual disability, autism spectrum- and attention deficit hyperactivity disorder-related features, self-injurious and physical aggressive behaviors, sleep–wake disorders, and seizures. Findings of this review may facilitate optimization of management strategies in adults with SMS, and may guide future studies exploring late-onset psychiatric and neurological comorbidities in SMS.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006544","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":"A polygenic resilience score moderates the genetic risk for schizophrenia: Replication in 18,090 cases and 28,114 controls from the Psychiatric Genomics Consortium","authors":"Jonathan L. Hess,&nbsp;Manuel Mattheisen,&nbsp;the Schizophrenia Working Group of the Psychiatric Genomics Consortium,&nbsp;Tiffany A. Greenwood,&nbsp;Ming T. Tsuang,&nbsp;Howard J. Edenberg,&nbsp;Peter Holmans,&nbsp;Stephen V. Faraone,&nbsp;Stephen J. Glatt","doi":"10.1002/ajmg.b.32957","DOIUrl":"10.1002/ajmg.b.32957","url":null,"abstract":"<p>Identifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variants that protect high-risk unaffected individuals from SCZ, leading to derivation of the first-ever “polygenic resilience score” for SCZ (resilient controls <i>n</i> = 3786; polygenic risk score-matched SCZ cases <i>n</i> = 18,619). Here, we performed a replication study to verify the moderating effect of our polygenic resilience score on SCZ risk (OR = 1.09, <i>p</i> = 4.03 × 10⁻⁵) using newly released GWAS data from 23 independent case–control studies collated by the Psychiatric Genomics Consortium (PGC) (resilient controls <i>n</i> = 2821; polygenic risk score-matched SCZ cases <i>n</i> = 5150). Additionally, we sought to optimize our polygenic resilience-scoring formula to improve subsequent modeling of resilience to SCZ and other complex disorders. We found significant replication of the polygenic resilience score, and found that strict pruning of SNPs based on linkage disequilibrium to known risk SNPs and their linked loci optimizes the performance of the polygenic resilience score.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520885","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":"Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder","authors":"Nikki Hubers,&nbsp;Fiona A. Hagenbeek,&nbsp;René Pool,&nbsp;Sébastien Déjean,&nbsp;Amy C. Harms,&nbsp;Peter J. Roetman,&nbsp;Catharina E. M. van Beijsterveldt,&nbsp;Vassilios Fanos,&nbsp;Erik A. Ehli,&nbsp;Robert R. J. M. Vermeiren,&nbsp;Meike Bartels,&nbsp;Jouke Jan Hottenga,&nbsp;Thomas Hankemeier,&nbsp;Jenny van Dongen,&nbsp;Dorret I. Boomsma","doi":"10.1002/ajmg.b.32955","DOIUrl":"10.1002/ajmg.b.32955","url":null,"abstract":"<p>The evolving field of multi-omics combines data and provides methods for simultaneous analysis across several omics levels. Here, we integrated genomics (transmitted and non-transmitted polygenic scores [PGSs]), epigenomics, and metabolomics data in a multi-omics framework to identify biomarkers for Attention-Deficit/Hyperactivity Disorder (ADHD) and investigated the connections among the three omics levels. We first trained single- and next multi-omics models to differentiate between cases and controls in 596 twins (cases = 14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in-sample prediction through cross-validation. The multi-omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations of ADHD with glucocorticoid exposure and the transmembrane protein family <i>TMEM</i>, show that the DNA methylation of the <i>MAD1L1</i> gene associated with ADHD has a relation with parental smoking behavior, and present novel findings including associations between indirect genetic effects and CpGs of the <i>STAP2</i> gene. However, out-of-sample prediction in NTR participants (<i>N</i> = 258, cases = 14.3%) and in a clinical sample (<i>N</i> = 145, cases = 51%) did not perform well (range misclassification was [0.40, 0.57]). The results highlighted connections between omics levels, with the strongest connections between non-transmitted PGSs, CpGs, and amino acid levels and show that multi-omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"195 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.32955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927784","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}