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

{"title":"Discrepancy in Combined Genotype Distribution Data Between Two Related Studies of 5-HTTLPR and Posttraumatic Stress Disorder Risk","authors":"Vishnu Shivam","doi":"10.1002/ajmgb.70006","DOIUrl":"10.1002/ajmgb.70006","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 5","pages":"317-318"},"PeriodicalIF":1.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147392125","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":"Patient Perspectives on Psychiatric Polygenic Risk Scores in Reproductive Decision-Making and Polygenic Embryo Screening","authors":"Lauren A. Ginn,&nbsp;Amanda R. Merner,&nbsp;Page M. Trotter,&nbsp;Kaitlynn P. Craig,&nbsp;Abigail C. Martinez,&nbsp;Ana Lucía Battaglino,&nbsp;Dorit Barlevy,&nbsp;Daphne M. Ayton,&nbsp;Takahiro Soda,&nbsp;Eric A. Storch,&nbsp;Gabriel Lázaro-Muñoz,&nbsp;Stacey Pereira","doi":"10.1002/ajmg.b.70011","DOIUrl":"10.1002/ajmg.b.70011","url":null,"abstract":"<p>Polygenic risk scores (PRS) estimate individuals' genetic risk for developing multifactorial conditions. Recent genome-wide association studies have enabled development of psychiatric PRS, which hold potential to streamline diagnosis and treatment of psychiatric conditions. As individuals with mental illness often identify concern about passing on psychiatric conditions as a key factor in family planning, some may also seek to use psychiatric PRS in reproductive decisions like childbearing or embryo selection for in vitro fertilization. Despite calls for increased regulation, there remains no clinical consensus on the utility of psychiatric PRS in reproductive contexts. Therefore, we conducted semi-structured interviews of adults with psychiatric conditions (<i>n</i> = 29) to evaluate patient perspectives toward the tool's potential benefits and risks. Approximately half of participants would be interested in harnessing psychiatric PRS for reproductive purposes—including embryo screening and family planning—driven largely by desires to improve children's quality of life and seek empowerment while parenting. Others worried selecting against embryos with genetic risk for psychiatric disorders could exacerbate stigma. Regardless of personal stance, many noted using psychiatric PRS in reproductive decisions should be permissible for the general population. As psychiatric PRS continue to mature, patient views reported here can help inform their future in reproductive spaces.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 5","pages":"338-348"},"PeriodicalIF":1.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215547","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":"Commentary on Immune-Genomic Approaches to Schizophrenia: Highlighting IRF3, L3HYPDH, and Drug Repurposing Targets","authors":"Chih-Ping Lin,&nbsp;Lien-Chung Wei","doi":"10.1002/ajmgb.70009","DOIUrl":"10.1002/ajmgb.70009","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 5","pages":"315-316"},"PeriodicalIF":1.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346193","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":"Are There Causal Associations Between Obsessive-Compulsive Disorder and Cardiometabolic Phenotypes? A Genetic Correlation and Bi-Directional Mendelian Randomization Study","authors":"Robyn E. Wootton,&nbsp;James J. Crowley,&nbsp;Josep Pol-Fuster,&nbsp;Anna Holmberg,&nbsp;Christian Rück,&nbsp;Obsessive-Compulsive Disorder Working Group of the Psychiatric Genomics Consortium,&nbsp;David Mataix-Cols,&nbsp;Lorena Fernández de la Cruz","doi":"10.1002/ajmgb.70003","DOIUrl":"10.1002/ajmgb.70003","url":null,"abstract":"<p>In epidemiological studies, obsessive-compulsive disorder (OCD) is robustly associated with increased risk of cardiometabolic disorders, including cardiovascular diseases, type 2 diabetes, and obesity. However, the mechanisms behind these associations are unclear. We conducted genetic correlation analyses to explore shared genetic etiology and bi-directional summary-level Mendelian randomization (MR) to explore potential causal effects between genetic liability to OCD and 14 cardiometabolic phenotypes (e.g., coronary artery disease, blood pressure, body mass index [BMI]). If causal effects were observed, we planned to conduct multivariable MR to explore indirect effects via health behaviors. We found no evidence for genetic correlations between OCD and any of the cardiometabolic phenotypes under study, except for a negative correlation with BMI (rG = −0.123, SE = 0.029, <i>p</i> &lt; 0.001). Summary-level MR showed no evidence for causal effects. Therefore, multivariable MR was not conducted. We found limited evidence for shared genetic etiology or causal effects using the largest OCD GWAS to date. However, we were predominantly only powered to detect medium to large effects in the direction of OCD to cardiometabolic traits, leaving the possibility of smaller causal effects existing. Future studies with larger, more representative samples will help to further interpret findings.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 5","pages":"321-330"},"PeriodicalIF":1.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmgb.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961149","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":"Schizophrenic Phenotype and Therapeutic Course Associated With Chromosome 22q11.2 Deletion in a Cohort Without Prior Diagnosis of Chromosome 22q11.2 Deletion Syndrome","authors":"Micha Gawlik,&nbsp;Paul Schneider,&nbsp;Bruno Pfuhlmann,&nbsp;Jürgen Deckert","doi":"10.1002/ajmgb.70008","DOIUrl":"10.1002/ajmgb.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Chromosome 22q11.2 deletion is the greatest single genetic factor predisposing to schizophrenia. The prevalence of schizophrenia reported ranges from 2% to 30% in patients with chromosome 22q11.2 deletion syndrome with a still discussed phenotype. In the present study 1177 patients diagnosed with schizophrenia, schizoaffective disorder or affective disorder according to ICD-10 criteria, none of which had been diagnosed with chromosome 22q11.2 deletion syndrome before, were screened for the chromosome 22q11.2 deletion or duplication applying TaqMan real-time PCR. In six patients a deletion was found. The prevalence of the chromosome 22q11.2 deletion in the study population was 0.5%. According to ICD-10, three patients were diagnosed with paranoid schizophrenia and three with schizoaffective disorder. Applying the differentiated criteria of Karl Leonhard, four patients were diagnosed with affect-laden paraphrenia. Patients were treated with antipsychotics with varying success and the course of the disease ranged from full remission to severe residuum. Given the relevant prevalence of chromosome 22q11.2 deletion in an unselected population like the present one, a general screening of schizophrenic patients is discussed given the potentially severe, but treatable symptoms of the syndrome.</p>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 5","pages":"331-337"},"PeriodicalIF":1.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134015","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148063288","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":"Genetic Underpinnings of Obsessive–Compulsive Disorder With and Without Tics: Implications of Genetic Heterogeneity on Clinical Management","authors":"Jade-Jocelyne Zouki,&nbsp;Weng Tong Wu,&nbsp;Anthea Stylianakis,&nbsp;Valsamma Eapen","doi":"10.1002/ajmg.b.33068","DOIUrl":"10.1002/ajmg.b.33068","url":null,"abstract":"<div>\u0000 \u0000 <p>The exact genetic mechanisms and link between obsessive–compulsive disorder (OCD) and tics/Tourette syndrome are not fully understood. This narrative review aims to summarize the literature examining whether the clinical phenotypes of OCD and OCD + tics (tic-related OCD) represent distinct entities and how this relates to their genetic underpinnings. Systematic searches were conducted in MEDLINE Complete and Embase databases to identify studies published since the Diagnostic and Statistical Manual 5th Edition introduced the category of OCD with and without tics in 2013. Articles reporting on family cohort studies, linkage and epigenetic analyses, and genome-wide association studies involving patients with OCD and/or tic-related OCD were included. While the studies have highlighted significant genetic heterogeneity, there is some evidence to suggest the role of serotonergic, glutamatergic, and dopaminergic systems, with the latter playing a significant role in the genesis of tic spectrum symptoms, which may have implications for choice of pharmacological management in those with OCD + tics. Given the significant genetic heterogeneity and consequent phenotypic variations, future research delineating homogeneous subgroups is needed, including longitudinal studies that examine whether the clinical phenotypes of the OCD/tic spectrum of conditions “breed true” in offspring, which may have implications for clinical assessment and management.</p>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 3","pages":"159-179"},"PeriodicalIF":1.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566629","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":"Black EquaLity in OCD NeuroGenomics (BELONG): Study Protocol","authors":"Iasha J. Williams,&nbsp;Dalia Y. Marquez,&nbsp;Kara E. Lopez-lengowski,&nbsp;Malini Bommiasamy,&nbsp;Ogechi “Cynthia” Onyeka,&nbsp;Slayton J. Underwood,&nbsp;Juliana E. Avery,&nbsp;Jacob Gluckman,&nbsp;Thariana Pichardo,&nbsp;Rhea Chandler,&nbsp;Yulu Brown,&nbsp;Katie Mangen,&nbsp;Emma Grace Choplin,&nbsp;Black EquaLity in OCD NeuroGenomics (BELONG) Study Team,&nbsp;Sonyia C. Richardson,&nbsp;Joseph D. Buxbaum,&nbsp;Eric A. Storch,&nbsp;James J. Crowley,&nbsp;Sidney H. Hankerson,&nbsp;Dorothy E. Grice","doi":"10.1002/ajmgb.70002","DOIUrl":"10.1002/ajmgb.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%–3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address this gap in understanding, we established the Black EquaLity in OCD NeuroGenomics (BELONG) study (https://belongocd.com/). BELONG aims to collect DNA and clinical data from 1250 richly phenotyped OCD cases of African ancestry in a culturally sensitive manner. In addition, BELONG includes the collection of parental DNA samples for trio-based analyses and unrelated matched controls for case–control analysis. DNA samples will be sequenced using optimized approaches that will allow us to examine both rare and common genome-wide variation to identify OCD risk genes. We will also meta-analyze these data with other existing OCD genomic data. Overall, BELONG will increase the representation of Black Americans in OCD genetic research, which is necessary to generalize precision medicine discoveries in psychiatric genetics.</p>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 3","pages":"194-204"},"PeriodicalIF":1.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961093","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":"Longitudinal Behavior Phenotype Hallmarks in RNU4-2 Syndrome: Implications for Clinical Management","authors":"Paola Francesca Ajmone,&nbsp;Claudia Rigamonti,&nbsp;Francesca Brasca,&nbsp;Donatella Milani,&nbsp;Chiara Ranci Ortigosa,&nbsp;Maria Iascone,&nbsp;Lucrezia Goisis,&nbsp;Annalaura Torella,&nbsp;Maria Antonella Costantino","doi":"10.1002/ajmgb.70004","DOIUrl":"10.1002/ajmgb.70004","url":null,"abstract":"<p>Pathogenic variants in the non-coding spliceosomal gene RNU4-2 underlie ReNU syndrome, one of the most prevalent monogenic causes of neurodevelopmental disorders, accounting for ~0.4% of cases. Despite increasing recognition, little is known about the longitudinal behavioral and neuropsychiatric phenotype of affected individuals. We report two patients with RNU4-2 variants, providing a comprehensive description of their developmental trajectories from infancy to adolescence. Both exhibited global developmental delay, impaired adaptive functioning, and significant language deficits. Distinctive features included persistent attention deficits and Autistic Spectrum Disorder, which emerged as hallmarks of the Syndrome. Case-specific differences were notable: one patient developed self-injurious behavior and social anxiety during adolescence, while the other presented with epilepsy and structural brain anomalies. Neuroimaging revealed convergent features, including white matter reduction, corpus callosum thinning, and ventricular dysmorphisms. Our findings highlight the importance of early, individualized interventions, with particular emphasis on augmentative and alternative communication strategies and cognitive-behavioral approaches to mitigate communicative frustration, behavioral dysregulation, and social anxiety. This study provides the first longitudinal neuropsychiatric characterization of RNU4-2-related disorder, delineating clinical hallmarks, and therapeutic windows. A better understanding of developmental trajectories in this condition is essential to optimize patient management and improve long-term outcomes.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 3","pages":"205-211"},"PeriodicalIF":1.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmgb.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183964","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 Variants Identified in Families With SNX27-Related Neurodevelopmental Disorder, Aiding in Characterizing Its Genotypic and Phenotypic Spectrum","authors":"Tayyaba Shan,&nbsp;Abrar Hussain,&nbsp;Anushree Acharya,&nbsp;Mulazim Hussain,&nbsp;Yumei Li,&nbsp;Hafiz Muhammad Jafar Hussain,&nbsp;Kiran Afshan,&nbsp;Suzanne M. Leal,&nbsp;Rui Chen,&nbsp;Asif Mir,&nbsp;Isabelle Schrauwen,&nbsp;Sabika Firasat","doi":"10.1002/ajmgb.70005","DOIUrl":"10.1002/ajmgb.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 <i>Sorting Nexin 27 (SNX27)</i>, a key regulator of synaptic receptor trafficking and endosomal recycling, has been implicated in maintaining synaptic homeostasis and cognitive function. To date, variants in <i>SNX27</i> have been reported in a small number of patients across three publications with severe neurodevelopmental phenotypes. However, the genetic and functional landscape of <i>SNX27</i>-related disorders remains poorly understood, and further evidence is needed to confirm its association with disease and to better delineate the associated phenotype. Two unrelated Pakistani families with a total of five affected individuals segregating a neurodevelopmental disorder were investigated via exome or genome sequencing. This revealed a novel homozygous frameshift variant in family I [NM_001330723.2: c.75dup; p. (Ser26Valfs*85)], predicted to be targeted by nonsense-mediated decay. In family II, a novel homozygous missense variant [NM_001330723.2: c.929 T&gt;C; p. (Met310Thr)] was found within the FERM-like region of the SNX27 protein, which is critical for retromer complex interaction. Comparison of five cases described in this study with previously reported six cases reinforces the presence of consistent “core” clinical features—global developmental delay, intellectual disability, speech delay, behavioral abnormalities, seizures, and motor dysfunction in all assessed cases. Other features such as dental anomalies, failure to thrive, and dysmorphisms occurred variably in few. Affected individuals with predicted loss-of-function variants typically presented with a more severe phenotype. Thus, core features of <i>SNX27</i>-related neurodevelopmental disorders (NDDs) are intellectual disability, developmental, and speech delays. This study, alongside prior reports, augments the genetic and phenotypic spectrum of <i>SNX27</i>-associated NDDs. The novel frameshift variant p.(Ser26Valfs*85) is predicted to severely disrupt SNX27 function, causing profound neurodevelopmental impairment, whereas the missense p.(Met310Thr) in the FERM-like region is associated with a milder phenotype. Comparative analyses with previous reports reveal a spectrum from early lethality to long-term survival with intellectual disability in <i>SNX27</i>-linked families. These findings underscore the importance of <i>SNX27</i> in neurodevelopment and further validate its link to a neurodevelopmental disorder.</p>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 3","pages":"212-221"},"PeriodicalIF":1.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088724","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}