NPJ Genomic Medicine最新文献

{"title":"Highly efficient capture approach for the identification of diverse inherited retinal disorders.","authors":"Hsiao-Jung Kao, Ting-Yi Lin, Feng-Jen Hsieh, Jia-Ying Chien, Erh-Chan Yeh, Wan-Jia Lin, Yi-Hua Chen, Kai-Hsuan Ding, Yu Yang, Sheng-Chu Chi, Ping-Hsing Tsai, Chih-Chien Hsu, De-Kuang Hwang, Hsien-Yang Tsai, Mei-Ling Peng, Shi-Huang Lee, Siu-Fung Chau, Chen Yu Chen, Wai-Man Cheang, Shih-Jen Chen, Pui-Yan Kwok, Shih-Hwa Chiou, Mei-Yeh Jade Lu, Shun-Ping Huang","doi":"10.1038/s41525-023-00388-3","DOIUrl":"10.1038/s41525-023-00388-3","url":null,"abstract":"<p><p>Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"4"},"PeriodicalIF":5.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.","authors":"Yusuph Mavura, Nuriye Sahin-Hodoglugil, Ugur Hodoglugil, Mark Kvale, Pierre-Marie Martin, Jessica Van Ziffle, W Patrick Devine, Sara L Ackerman, Barbara A Koenig, Pui-Yan Kwok, Mary E Norton, Anne Slavotinek, Neil Risch","doi":"10.1038/s41525-023-00385-6","DOIUrl":"10.1038/s41525-023-00385-6","url":null,"abstract":"<p><p>It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis. Continental/subcontinental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov-Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. We observed no reduction in overall DY associated with any genetic ancestry (African, Native American, East Asian, European, Middle Eastern, South Asian). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"1"},"PeriodicalIF":5.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer.","authors":"Ilya G Serebriiskii, Valerii A Pavlov, Grigorii V Andrianov, Samuel Litwin, Stanley Basickes, Justin Y Newberg, Garrett M Frampton, Joshua E Meyer, Erica A Golemis","doi":"10.1038/s41525-023-00384-7","DOIUrl":"10.1038/s41525-023-00384-7","url":null,"abstract":"<p><p>Somatic PTEN mutations are common and have driver function in some cancer types. However, in colorectal cancers (CRCs), somatic PTEN-inactivating mutations occur at a low frequency (~8-9%), and whether these mutations are actively selected and promote tumor aggressiveness has been controversial. Analysis of genomic data from ~53,000 CRCs indicates that hotspot mutation patterns in PTEN partially reflect DNA-dependent selection pressures, but also suggests a strong selection pressure based on protein function. In microsatellite stable (MSS) tumors, PTEN alterations co-occur with mutations activating BRAF or PI3K, or with TP53 deletions, but not in CRC with microsatellite instability (MSI). Unexpectedly, PTEN deletions are associated with poor survival in MSS CRC, whereas PTEN mutations are associated with improved survival in MSI CRC. These and other data suggest use of PTEN as a prognostic marker is valid in CRC, but such use must consider driver mutation landscape, tumor subtype, and category of PTEN alteration.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"40"},"PeriodicalIF":5.3,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13.","authors":"Prince Jacob, Hillevi Lindelöf, Cecilie F Rustad, Vernon Reid Sutton, Shahida Moosa, Prajna Udupa, Anna Hammarsjö, Gandham SriLakshmi Bhavani, Dominyka Batkovskyte, Kristian Tveten, Ashwin Dalal, Eva Horemuzova, Ann Nordgren, Emma Tham, Hitesh Shah, Else Merckoll, Laura Orellana, Gen Nishimura, Katta M Girisha, Giedre Grigelioniene","doi":"10.1038/s41525-023-00380-x","DOIUrl":"10.1038/s41525-023-00380-x","url":null,"abstract":"<p><p>Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, retaining the same radiographic pattern of spondylar- and epi-metaphyseal dysplasia, but with varying severity of the hip and knee deformities. Two new missense variants, c.548 G>A, p.(Arg183His) and c.569 G>T, p.(Arg190Leu), and a previously known splice variant c.477+1G>A were identified, confirming mutational clustering in a highly specific RNA binding motif. Structural analysis and interpretation of the variants' impact on the protein suggests that disruption of extra-ribosomal functions of the protein through binding of mRNA may play a role in the skeletal phenotype of SEMD-RPL13. In addition, we present gonadal and somatic mosaicism for the condition.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"39"},"PeriodicalIF":5.3,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Populational pan-ethnic screening panel enabled by deep whole genome sequencing.","authors":"Linfeng Yang, Zhe Lin, Yong Gao, Jianguo Zhang, Huanhuan Peng, Yaqing Li, Jingang Che, Lijian Zhao, Jilin Zhang","doi":"10.1038/s41525-023-00383-8","DOIUrl":"10.1038/s41525-023-00383-8","url":null,"abstract":"<p><p>Birth defect is a global threat to the public health systems. Mitigating neonatal anomalies is hampered by elusive molecular mechanisms of pathogenic mutations and poor subsequent translation into preventative measures. Applying appropriate strategies in China to promote reproductive health is particularly challenging, as the Chinese population compromises complex genomic diversity due to the inclusion of many ethnic groups with distinct genetic backgrounds. To investigate and evaluate the feasibility of implementing a pan-ethnic screening strategy, and guide future reproductive counselling, high-quality variants associated with autosome recessive (AR) diseases derived from the largest publicly available cohort of the Chinese population were re-analysed using a bottom-up approach. The analyses of gene carrier rates (GCRs) across distinct ethnic groups revealed that substantial heterogeneity existed potentially due to diverse evolutionary selection. The sampling population, sequencing coverage and underlying population structure contributed to the differential variants observed between ChinaMAP and the East Asian group in gnomAD. Beyond characteristics of GCR, potential druggable targets were additionally explored according to genomic features and functional roles of investigated genes, demonstrating that phase separation could be a therapeutic target for autosomal recessive diseases. A further examination of estimated GCR across ethnic groups indicated that most genes shared by at least two populations could be utilised to direct the design of a pan-ethnic screening application once sequencing and interpreting costs become negligible. To this end, a list of autosomal recessive disease genes is proposed based on the prioritised rank of GCR to formulate a tiered screening strategy.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"38"},"PeriodicalIF":5.3,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome.","authors":"Bengi Ruken Yavuz, M Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag","doi":"10.1038/s41525-023-00377-6","DOIUrl":"10.1038/s41525-023-00377-6","url":null,"abstract":"<p><p>Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers. As to NDD-associated mutations, in most cases, they are germline while cancer mutations are sporadic, emerging during life. However, somatic mosaicism can spur NDDs, and cancer-related mutations can be germline. NDDs and cancer share proteins, pathways, and mutations. Here we ask (i) exactly which features they share, and (ii) how, despite their commonalities, they differ in clinical outcomes. To tackle these questions, we employed a statistical framework followed by network analysis. Our thorough exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signaling strength as the key factor: strong signaling promotes cell proliferation in cancer, and weaker (moderate) signaling impacts differentiation in ASD. Thus, we suggest that signaling strength, not activating mutations, can decide clinical outcome.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"37"},"PeriodicalIF":4.7,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants.","authors":"Edwin K Silverman, Arthur Y Kim, Barry J Make, Elizabeth A Regan, Jarrett D Morrow, Craig P Hersh, James O'Brien, James D Crapo, Nadia N Hansel, Gerard Criner, Eric L Flenaugh, Douglas Conrad, Richard Casaburi, Russell P Bowler, Nicola A Hanania, R Graham Barr, Surya P Bhatt, Frank C Sciurba, Antonio Anzueto, MeiLan K Han, Charlene E McEvoy, Alejandro P Comellas, Dawn L DeMeo, Richard Rosiello, Jeffrey L Curtis, Tricia Uchida, Carla Wilson, P Pearl O'Rourke","doi":"10.1038/s41525-023-00379-4","DOIUrl":"10.1038/s41525-023-00379-4","url":null,"abstract":"<p><p>The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"36"},"PeriodicalIF":5.3,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients.","authors":"Maksym Zarodniuk, Alexander Steele, Xin Lu, Jun Li, Meenal Datta","doi":"10.1038/s41525-023-00381-w","DOIUrl":"10.1038/s41525-023-00381-w","url":null,"abstract":"<p><p>Excessive deposition of extracellular matrix (ECM) is a hallmark of solid tumors; however, it remains poorly understood which cellular and molecular components contribute to the formation of ECM stroma in central nervous system (CNS) tumors. Here, we undertake a pan-CNS analysis of retrospective gene expression datasets to characterize inter- and intra-tumoral heterogeneity of ECM remodeling signatures in both adult and pediatric CNS disease. We find that CNS lesions - glioblastoma in particular - can be divided into two ECM-based subtypes (ECM^hi and ECM^lo) that are influenced by the presence of perivascular stromal cells resembling cancer-associated fibroblasts (CAFs). Ligand-receptor network analysis predicts that perivascular fibroblasts activate signaling pathways responsible for recruitment of tumor-associated macrophages and promotion of cancer stemness. Our analysis reveals that perivascular fibroblasts are correlated with unfavorable response to immune checkpoint blockade in glioblastoma and poor patient survival across a subset of CNS tumors. We provide insights into new stroma-driven mechanisms underlying immune evasion and immunotherapy resistance in CNS tumors like glioblastoma, and discuss how targeting these perivascular fibroblasts may prove an effective approach to improving treatment response and patient survival in a variety of CNS tumors.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"35"},"PeriodicalIF":5.3,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population.","authors":"Anne Slavotinek, Shannon Rego, Nuriye Sahin-Hodoglugil, Mark Kvale, Billie Lianoglou, Tiffany Yip, Hannah Hoban, Simon Outram, Beatrice Anguiano, Flavia Chen, Jeremy Michelson, Roberta M Cilio, Cynthia Curry, Renata C Gallagher, Marisa Gardner, Rachel Kuperman, Bryce Mendelsohn, Elliott Sherr, Joseph Shieh, Jonathan Strober, Allison Tam, Jessica Tenney, William Weiss, Amy Whittle, Garrett Chin, Amanda Faubel, Hannah Prasad, Yusuph Mavura, Jessica Van Ziffle, W Patrick Devine, Ugur Hodoglugil, Pierre-Marie Martin, Teresa N Sparks, Barbara Koenig, Sara Ackerman, Neil Risch, Pui-Yan Kwok, Mary E Norton","doi":"10.1038/s41525-023-00382-9","DOIUrl":"10.1038/s41525-023-00382-9","url":null,"abstract":"","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"34"},"PeriodicalIF":5.3,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity.","authors":"Na Zhu, Charles A LeDuc, Ilene Fennoy, Blandine Laferrère, Claudia A Doege, Yufeng Shen, Wendy K Chung, Rudolph L Leibel","doi":"10.1038/s41525-023-00376-7","DOIUrl":"10.1038/s41525-023-00376-7","url":null,"abstract":"<p><p>Bassoon (BSN) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo (PCLO) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity. We found that rare heterozygous predicted loss of function (pLoF) variants in BSN are associated with higher BMI with p-value of 3.6e-12 in the UK biobank cohort. Additionally, we identified two individuals (one of whom has a de novo variant) with a heterozygous pLoF variant in a cohort of early onset or extreme obesity and report the clinical histories of these individuals with non-syndromic obesity with no history of neurobehavioral or cognitive disability. The BMI association was replicated in the All of Us whole genome sequencing data. Heterozygous pLoF BSN variants constitute a new etiology for obesity.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"33"},"PeriodicalIF":4.7,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}