American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics最新文献

{"title":"Cross-Ancestry Polygenic Prediction of Bipolar Disorder and Obsessive-Compulsive Disorder in India.","authors":"Bharath Holla, Suhas Ganesh, Jayant Mahadevan, Reeteka Sud, Meghana Janardhanan, Srinivas Balachander, Swarna Buddha Nayok, Pavithra Jayasankar, Manuel Mattheisen, Nora Strom, Patrick F Sullivan, Hailiang Huang, Peter P Zandi, Janardhan Y C Reddy, Vivek Benegal, Sanjeev Jain, Meera Purushottam, Biju Viswanath","doi":"10.1002/ajmg.b.70037","DOIUrl":"https://doi.org/10.1002/ajmg.b.70037","url":null,"abstract":"<p><p>Most genetic studies of psychiatric disorders have been conducted predominantly in populations of European ancestry, limiting evidence for the transferability of polygenic scores (PGS) to other populations. This cross-sectional study evaluated the predictive performance of European-derived PGS for bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in an Indian sample. Participants (N = 2531) included individuals with BD (N = 463), OCD (N = 554), and controls (N = 1514) recruited from hospital- and community-based samples. Genotyping was performed using the Illumina Global Screening Array. PGS were derived from the summary statistics of European-ancestry genome-wide association studies using two Bayesian methods, PRS-CS-auto and SBayesRC. Principal component analyses demonstrated genetic overlap of the study population with other South Asian populations. BD PGS showed significant predictive performance, explaining approximately 6%-7% of liability-scale variance with PGS-only AUCs of ~0.71. OCD PGS showed lower but significant predictive performance, explaining ~2%-3% of variance with AUCs of approximately 0.59. Bayesian approaches showed better predictive performance than conventional clumping-and-thresholding. These findings demonstrate that European-derived psychiatric PGS can retain predictive information in an Indian population, although performance differed between disorders. The application of Bayesian PGS methods in this Indian cohort supports their utility for cross-ancestry prediction, while reinforcing the need for larger genomic studies in South Asian and other underrepresented populations.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149291876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Genetic and Biological Interconnections Between Neuroticism, Psychological Distress, Insomnia, and C-Reactive Protein: Insights From the UK Biobank.","authors":"Lydia M Li, Nina Adler, Cristina L Abbatangelo, Mark Wade, Esteban J Parra","doi":"10.1002/ajmg.b.70038","DOIUrl":"https://doi.org/10.1002/ajmg.b.70038","url":null,"abstract":"<p><p>Psychobehavioral and physical health traits often co-occur. Although previous studies have identified associations between neuroticism, psychological distress, insomnia, and inflammatory biomarkers such as C-reactive protein (CRP), it remains unclear whether there is a genetic basis to these associations, and which biological pathways are involved. This study aimed to explore pleiotropy between psychobehavioural and physical traits and examine underlying biological pathways. To identify shared SNPs, we applied CPASSOC SHet and genomic SEM to GWAS summary statistics from the UK Biobank (Neale Lab; N_neuroticism = 293,006; N_{doctor visits for distress} = 358,693; N_insomnia = 360,738; N_CRP = 358,693). Pathway enrichment analyses were done to explore relevant biological pathways based on positional and eQTL annotations. We used colocalization data to evaluate sharing of genetic signals between pairs of traits. Genetic correlations were moderate to high among neuroticism, distress visits, and insomnia, but low between CRP and each psychobehavioral trait. In the multitrait analyses, we did not observe any genomic region with genome-wide significant variants for all traits, although we identified a few regions with markers that reached genome-wide significance in the cross-trait analysis and had p-values < 0.001 for all traits. Enrichment analysis highlighted 8p23.1, a polymorphic inversion region enriched for immune and developmental genes. Colocalization supported multiple shared causal variants among psychobehavioral traits, with limited sharing with CRP. These findings suggest that co-occurrence between psychobehavioral and systemic inflammation traits is only weakly explained by shared common-variant genetics, emphasizing nongenetic mechanisms.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Factors Modifying the Link Between Genetic Risk for Autism and Developmental Milestones.","authors":"Liliana D'Alesio, Vishani Nimish Patel, McKenna Walsh, Erick Messias, Ping-I Lin","doi":"10.1002/ajmg.b.70040","DOIUrl":"https://doi.org/10.1002/ajmg.b.70040","url":null,"abstract":"<p><p>Although common genetic liability-quantified through polygenic risk scores (PRS)-accounts for substantial variance in autism spectrum disorder (ASD) liability, how prenatal environmental exposures interact with genetic predisposition to shape developmental outcomes remains poorly understood. Using the data from Autism Genetic Resource Exchange (AGRE), we examined whether maternal prenatal factors moderate the association between ASD PRS and developmental outcomes, including language delay, motor delay, and core ASD traits. In exploratory gene-environment interaction analyses, amniocentesis was a candidate positive moderator of the association between PRS and both language and motor delay, such that higher polygenic liability was associated with a greater likelihood of these delays among prenatally exposed children. First-trimester vaginal bleeding showed a similar positive interaction estimate for motor delay. Maternal use of over-the-counter (OTC) medications during pregnancy-predominantly acetaminophen, reported by 59.9% of OTC users-was associated with an inverse interaction estimate, corresponding to a decreased association between polygenic liability and language delay among exposed children. These observations suggest that several prenatal factors may modify the association between common genetic liability and developmental outcomes among autistic children and should be considered hypothesis-generating until replicated in larger, population-based cohorts. Replication in independent samples, together with analyses that address selection and confounding, will be required before these candidate gene-environment interactions can be interpreted as reflecting specific developmental mechanisms.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Liability for Major Psychiatric Disorders and Clinical Features of Schizophrenia.","authors":"Alessandro Serretti","doi":"10.1002/ajmg.b.70039","DOIUrl":"https://doi.org/10.1002/ajmg.b.70039","url":null,"abstract":"<p><p>Polygenic scores (PGS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD) are used to explain heterogeneity in schizophrenia, but European-derived scores applied in ancestrally mixed samples risk confounding by population structure. In the CATIE trial, we tested 3 a priori directional hypotheses under one rule: covariate-adjusted model, one-tailed p, within-family false-discovery-rate correction. The primary sample was 407 participants of European ancestry, with principal components recomputed within it; scores were computed with PRS-CS. Higher BD-PGS predicted less improvement in PANSS Total (β = 1.69 per SD, one-tailed p = 0.036, q = 0.036) and earlier treatment discontinuation (HR = 1.16, 95% CI 1.004-1.340, q = 0.036); joint models with all three scores did not account for either effect. MDD-PGS and SCZ-PGS were unassociated with baseline symptoms. The four motor/behavioral item-level associations with SCZ-PGS detected in the ancestrally mixed sample (ρ = 0.11-0.14) did not survive European-only analysis, were not reproduced by removing 72 participants at random (permutation p ≤ 0.002), and reflect a score that differs by 1.5 SD between ancestry groups: population stratification. Effects are small and not clinically actionable; PGS-symptom associations from mixed samples should be treated as provisional until replicated within one ancestry.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Variants of Na⁺,K⁺-ATPase Associated With Neurological Disorders: A Systematic Review.","authors":"Giovana Kummer da Rosa, Leandro Rodrigo Ribeiro, Jéssica Lorena Bariviera, Mauro Schneider Oliveira","doi":"10.1002/ajmg.b.70035","DOIUrl":"https://doi.org/10.1002/ajmg.b.70035","url":null,"abstract":"<p><p>Neurological disorders encompass a wide range of severe symptoms and manifestations, many of which are associated with genetic variants that affect ionic homeostasis. Na⁺,K⁺-ATPase, a transmembrane enzyme responsible for maintaining electrochemical gradients in cells, plays a crucial role in neuronal excitability and brain function. The present review aimed to systematically identify and organize published data on Na⁺,K⁺-ATPase variants reported in human studies with neurological outcomes, compiling this information into a structured format. Variants in the ATP1A1 (α1) gene are associated with epilepsy, developmental delay, autism spectrum disorder, and Charcot-Marie-Tooth disease (CMT). Variants in the ATP1A2 (α2) gene are mainly associated with familial hemiplegic migraine type 2 (FHM2) and sporadic hemiplegic migraine (SHM), and epilepsy. Moreover, severe neurodevelopmental phenotypes such as polymicrogyria and microcephaly arise from biallelic ATP1A2 loss-of-function variants. ATP1A3 (α3) variants present the broadest phenotypic diversity, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), cerebellar ataxia, childhood-onset schizophrenia, and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS) syndrome. Furthermore, the Gly41Arg variant in the FXYD2 gene is implicated in isolated dominant hypomagnesemia (IDH) with possible neurological manifestations. The structured compilation presented here consolidates data from 61 studies and covers 123 distinct variants across four Na⁺,K⁺-ATPase subunits, providing an annotated reference that may help future research.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extending the ATP9A-Related Phenotypic Spectrum: Indication of Schizophrenia Susceptibility.","authors":"Camille Verebi, Céline Louveau, Bertrand Diebold, Natacha Gaitch, Arnaud Hubas, Martine Gautier Vallee, Jérôme Champ, Anais L'Haridon, Sophie Georgin Lavialle, Boris Chaumette, Thierry Bienvenu","doi":"10.1002/ajmg.b.70036","DOIUrl":"https://doi.org/10.1002/ajmg.b.70036","url":null,"abstract":"<p><p>ATP9A, which belongs to the P4-ATPase family of proteins, is involved in the efficient transport of vesicles from the Golgi apparatus to the plasma membrane, as well as the release of extracellular vesicles from human cells. In 2021, a loss-of-function variant of this gene was identified as being associated with a recessive neurodevelopmental disorder characterized by severe intellectual disability, motor delay, speech impairment, impaired fine motor skills, and behavioral anomalies, such as attention deficit hyperactivity disorder and aggressive behavior. Furthermore, in 2025, a de novo missense variant in the same gene was identified as being associated with a dominant neurodevelopmental disorder exhibiting a very similar phenotype. In this study, we identified three novel de novo variants in the ATP9A gene in two unrelated patients diagnosed with schizophrenia or schizoaffective disorder by performing trio short-read whole-genome sequencing (WGS). One individual presenting with severe psychosis was found to carry a de novo synonymous variant, c.2113C>T, p.(Leu705=), in the ATP9A gene. All software predicted that this variant would alter the 5' splice site of intron 19. An intron minigene assay showed that it disrupts normal gene splicing. The second individual, who had refractory schizophrenia, was found to carry two variants in the ATP9A gene: a de novo nonsense variant c.1740C>G, p.(Tyr580*), and a large de novo deletion including exons 18 and 19 of the ATP9A gene (GRCh38:g.51517885_51628972del). We demonstrated the presence of these two rare variants in cis using long-range PCR. Our findings suggest that individuals with ATP9A gene variants may exhibit severe psychiatric disorders, regardless of the inheritance pattern. ATP9A plays a role in neuronal development and may therefore be involved in the development of psychiatric disorders. This warrants specific attention to heterozygous individuals. Our results reinforce the data obtained in the largest exome meta-analysis conducted by the SCHEMA consortium. That study showed that protein-truncating and pathogenic missense variants in ATP9A were significantly associated with schizophrenia (p = 0.000372; odds Ratio = 5.48).</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Molecular Genetic Classes on Behavior in Prader-Willi Syndrome.","authors":"Ranim Mahmoud, Merlin G Butler, Wai Park, Jennifer L Miller, Daniel J Driscoll, June-Anne Gold, Virginia Kimonis","doi":"10.1002/ajmg.b.70034","DOIUrl":"https://doi.org/10.1002/ajmg.b.70034","url":null,"abstract":"<p><p>A wide range of behavioral phenotypes has been described in PWS patients including autism spectrum disorder (ASD). The prevalence of behavioral disorders was studied in 292 participants over 3 years with genetically confirmed PWS (N = 164 females and N = 128 males) with deletion (N = 182) and mUPD (maternal uniparental disomy) (N = 99). The prevalence of ASD, and other behavioral disorders was tested for association with gender, genetic subtypes, and growth hormone (GH) treatment. The prevalence of ASD in PWS individuals was 19.5%, in concordance with previous studies at 25%. The frequency of ADHD was 10.7%. The mean age at diagnosis for ASD, ADHD, and disruptive behavior was 14.9 ± 10.5, 9.3 ± 5.9, and 19.6 ± 14 years, respectively. There was no statistically significant difference in the prevalence of ASD and ADHD between deletion and UPD subjects, and between GH-treated and non-treated subjects. Patients with mUPD had higher frequencies of anxiety than those with deletions (p = 0.001). GH-treated participants had a lower frequency of depression and a higher frequency of anxiety than non-treated participants (p = 0.04, p = 0.02, respectively). This is the largest study to evaluate an association between genetically confirmed PWS and ASD. We found no significant differences in the frequency of ASD and other behavioral disorders across the genetic groups and GH treatment.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Glutamatergic and Dopaminergic Genes in Resistant Schizophrenia: A Systematic Review.","authors":"Maria Teresa Moreno-Calle, Silvia Iñiguez-Barrio, Maria Aurora Arrue, Leire Erkoreka","doi":"10.1002/ajmg.b.70031","DOIUrl":"https://doi.org/10.1002/ajmg.b.70031","url":null,"abstract":"<p><p>Psychosis is a heterogeneous disorder, with approximately one-third of patients experiencing treatment resistance, predominantly among individuals diagnosed with Schizophrenia. Treatment-resistant schizophrenia (TRS) may stem from a distinct biological signature, involving abnormalities in the dopaminergic and glutamatergic systems. However, generalizing research findings has been challenged by inconsistent definition of resistance. Following PRISMA guidelines, a systematic literature search was conducted across four databases (PubMed, Embase, PsycINFO, and Medline) utilizing the treatment response and resistance in psychosis criteria to standardize the definition of resistance. The objective was to identify concordant genetic findings in key dopaminergic and glutamatergic pathways related to TRS, ultimately seeking genetic markers for diagnosis. Eighteen studies of moderate quality were included. The findings tentatively implicate specific glutamatergic and dopaminergic abnormalities in treatment-resistant patients, particularly involving loci within the DRD2, COMT, and NMDAR genes. Despite this concordance, the generalizability of results remains limited by factors like patient heterogeneity, varied study designs, and differences in treatment protocols. Candidate gene studies implicated genes from both dopaminergic and glutamatergic pathways in TRS but demonstrated genetic heterogeneity. Future research should advance beyond candidate-gene studies to use more robust methods, such as polygenic risk scoring, to improve the predictive accuracy of markers characterizing the TRS diagnosis.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient and Family Reported Clinical Picture of IRF2BPL-Related Disorders.","authors":"Zoe Goldstone-Joubert, Danielle M Pascual, Laurie Anne Bailey, Loren D M Peña, Paul C Marcogliese","doi":"10.1002/ajmg.b.70032","DOIUrl":"https://doi.org/10.1002/ajmg.b.70032","url":null,"abstract":"<p><p>IRF2BPL-related disorder is a neurodevelopmental disorder caused by heterozygous variants in the IRF2BPL (Interferon Regulatory Factor 2 Binding Protein-Like) gene. The few reports available in the literature suggest that common symptoms include developmental delay, intellectual disability, and developmental regression. Although emerging reports suggest broad relationships between variant class/location and severity, genotype-phenotype correlations remain incompletely defined. We developed a retrospective and prospective patient-reported survey to assess diagnostic information, presenting symptoms, and longitudinal follow-up of neurological symptoms for up to two years. Clinical information was available for all 32 participants and was highly variable in regards to age at symptom onset, severity of neurologic manifestations, and progressivity. For 27 of the 32 participants, diagnostic genetic test results were available. Genetic mutation analysis revealed 22 individuals with truncating variants and five participants with unique missense variants in IRF2BPL. The study data support the hypothesis that IRF2BPL missense variants are associated with a less severe disease presentation and progression than participants with truncating variants. The purpose of this study is to further define IRF2BPL-related disorder and provide more clinical and molecular insight into this ultra-rare disease.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trace Elements Genetics: A Potential Role in Treatment-Resistant Major Psychoses and Related Traits?","authors":"Chiara Fabbri, Alessandro Serretti, Marco Menchetti, Benedetta Vai, Francesco Benedetti, Lidia Fortaner-Uyà, Concetta Crisafulli","doi":"10.1002/ajmg.b.70030","DOIUrl":"https://doi.org/10.1002/ajmg.b.70030","url":null,"abstract":"<p><p>Trace elements are pivotal to key biological processes, with possible effects on psychopathology. We investigated the hypothesis of shared genetic factors between trace elements levels, treatment resistance and related traits. We used genome-wide summary statistics for trace elements blood concentration, treatment-resistant depression (TRD), treatment-resistant schizophrenia (TRS), and related traits, including anhedonia, neurovegetative symptoms, suicidal ideation, and cognition. Cross-trait genetic correlations (r_g) were estimated with High-Definition Likelihood with Bonferroni correction (α = 0.0031). Significant r_g were tested by two-sample Mendelian randomization (MR) and polygenic scores (PGSs) in UK Biobank. We found an inverse r_g between zinc and TRD (r_g = -0.20, SE = 0.07, p = 4.52 × 10^-3), and a consistent non-significant trend for TRS (p = 0.06). Copper correlated positively with appetite/weight gain (r_g = 0.11, SE = 0.036, p = 0.0026). MR provided no evidence of causal effects of zinc levels on TRD or copper levels on appetite/weight gain, possibly reflecting weak instruments. The PGS of zinc was not associated with TRD, nor the PGS of copper with appetite/weight gain, in UK Biobank (n = 15,927 and n = 35,849, respectively). Our results suggested genetic correlations involving zinc and TRD, copper and neurovegetative symptomatology, without support for a causal model or predictive effect of the respective PGSs. This may suggest limited power, residual confounding, or alternative shared genetic architectures.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}