RESUMO
Chatbots, web-based artificial intelligence tools that simulate human conversation, are increasingly in use to support many areas of genomic medicine. However, patient preferences towards using chatbots across the range of clinical settings are unknown. We conducted a qualitative study with individuals who underwent genetic testing for themselves or their child. Participants were asked about their preferences for using a chatbot within the genetic testing journey. Thematic analysis employing interpretive description was used. We interviewed 30 participants (67% female, 50% 50 + years). Participants considered chatbots to be inefficient for very simple tasks (e.g., answering FAQs) or very complex tasks (e.g., explaining results). Chatbots were acceptable for moderately complex tasks where participants perceived a favorable return on their investment of time and energy. In addition to achieving this "sweet spot," participants anticipated that their comfort with chatbots would increase if the chatbot was used as a complement to but not a replacement for usual care. Participants wanted a "safety net" (i.e., access to a clinician) for needs not addressed by the chatbot. This study provides timely insights into patients' comfort with and perceived limitations of chatbots for genomic medicine and can inform their implementation in practice.
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Inteligência Artificial , Serviços em Genética , Criança , Humanos , Feminino , Masculino , Testes Genéticos , Preferência do Paciente , SoftwareRESUMO
Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.
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COVID-19 , Aconselhamento Genético , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/genética , SARS-CoV-2/genética , Genômica/métodos , GenótipoRESUMO
We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians. Reanalysis of clinically relevant genes identified diagnoses in 4% (13/287); four were missed by clinical testing. Translational research methods, including analysis of novel candidate genes, identified candidates in 21% (61/287). Of these, 24 families have additional evidence through data sharing to support likely diagnoses (8% of cohort). This study indicates few diagnoses are missed by clinical laboratories, the incremental gain from reanalysis of clinically-relevant genes is modest, and the highest yield comes from validation of novel disease-gene associations. Future implementation of translational research methods, including continued reporting of compelling genes of uncertain significance by clinical laboratories, should be considered to maximize diagnoses.
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Testes Genéticos , Humanos , Testes Genéticos/métodos , Ontário/epidemiologia , Sequenciamento do ExomaRESUMO
BACKGROUND: Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology. METHODS: Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing. RESULTS: Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results. CONCLUSIONS: This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.
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Sequenciamento do Exoma , Predisposição Genética para Doença , Doenças não Diagnosticadas/diagnóstico , Sequenciamento Completo do Genoma , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Exoma/genética , Feminino , Testes Genéticos/tendências , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Doenças não Diagnosticadas/epidemiologia , Doenças não Diagnosticadas/genética , Adulto JovemRESUMO
Osteopathia striata with cranial sclerosis (OSCS; OMIM# 300373) is a rare X-linked disorder caused by mutations of the AMER1 gene. OSCS is traditionally considered a skeletal dysplasia, characterized by cranial sclerosis and longitudinal striations in the long bone metaphyses. However, OSCS affects many body systems and varies significantly in phenotypic severity between individuals. This case series focuses on the phenotypic presentation and development of individuals with OSCS. We provide an account of 12 patients with OSCS, ranging from 5 months to 38 years of age. These patients were diagnosed with OSCS after genetic testing confirmed pathogenic mutations in AMER1. Patient consent was obtained for photos and participation. Data were collected regarding perinatal history, dysmorphic features, and review of systems. This case series documents common facial dysmorphology, as well as rare extraskeletal features of OSCS, including two patients with intestinal malrotation and two patients with pyloric stenosis. We share four apparently nonmosaic males with OSCS (one de novo and three maternal variants). We also provide a clinical update on a patient who was previously published by Chénier et al. (2012). American Journal of Medical Genetics Part A, 158, 2946-2952. More research is needed to investigate the links between genotype and phenotype and assess the long-term comorbidities and overall quality of life of individuals with OSCS.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Osteosclerose/genética , Crânio/patologia , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Canadá , Criança , Pré-Escolar , Feminino , Genes Ligados ao Cromossomo X , Humanos , Lactente , Masculino , Anormalidades Musculoesqueléticas , Mutação/genética , Osteosclerose/diagnóstico , Osteosclerose/patologia , Fenótipo , Gravidez , Qualidade de Vida , Crânio/diagnóstico por imagem , Adulto JovemRESUMO
Carnitine Uptake Defect (CUD) is an autosomal recessive disorder due to mutations in the SLC22A5 gene. Classically patients present in infancy with profound muscle weakness and cardiomyopathy with characteristic EKG findings. Later presentations include recurrent hypoketotic hypoglycemia, proximal limb girdle myopathy,and/or recurrent muscle pain. Newborn screening detects most of these clinical variants but in addition has identified maternal CUD often in asymptomatic women. We describe a family ascertained through 3 newborn screening (NBS) positive infants found to be unaffected themselves but in whom the mothers (sisters) were affected. There were also two affected children born to an affected male and his heterozygous wife who were false negatives on NBS but had increased fractional excretion of free carnitine in the urine. Analysis on a Next Generation Sequencing panel specifically designed to fully cover newborn screening disease targets showed a homozygous change in the five probands (SLC22A5; NM_003060:c.-149G > A; p.?). The mutation segregates with the CUD within the family. It is in the 5' UTR and has a frequency within the gnomAd database of 0.001198. Plasma carnitine was decreased and fractional excretion of free carnitine was increased in all affected individuals. Functional carnitine uptake studies in cultured skin fibroblasts of one proband showed carnitine uptake at the 5 µM concentration to be 6% of controls. Relative expression of OCTN2 mRNA to beta-actin mRNA by qRT-PCR was increased in a proband relative to controls by a factor of 465-fold. Western blotting revealed a 120 kDa protein band, as well as a weaker 240 kDa band in the proband, the significance of which is unknown at this time.
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Regiões 5' não Traduzidas/genética , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Carnitina/sangue , Carnitina/deficiência , Hiperamonemia/diagnóstico , Hiperamonemia/genética , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Membro 5 da Família 22 de Carreadores de Soluto/genética , Actinas/genética , Actinas/metabolismo , Transporte Biológico Ativo/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Carnitina/genética , Carnitina/metabolismo , Células Cultivadas , Criança , Pré-Escolar , Feminino , Fibroblastos/metabolismo , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Hiperamonemia/metabolismo , Hiperamonemia/fisiopatologia , Lactente , Recém-Nascido , Masculino , Doenças Musculares/metabolismo , Doenças Musculares/fisiopatologia , Mutação , Triagem Neonatal , Linhagem , Pele/citologia , Pele/metabolismo , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Sequenciamento do ExomaRESUMO
OBJECTIVE: There is a paucity of literature on genetic diagnosis in psychiatric populations, particularly the vulnerable population of patients with concomitant neurodevelopmental disorder (NDD). In this cross-sectional study, we investigated the genetic diagnostic rate in 151 adult psychiatric patients from two centers in Ontario, Canada, including a large subset (73.5%) with concurrent NDD, and performed phenotypic analysis to determine the strongest predictors for the presence of a genetic diagnosis. METHOD: Patients 16 years of age or older and affected with a psychiatric disorder plus at least one of NDD, neurological disorder, congenital anomaly, dysmorphic features, or family history of NDD were recruited through the genetics clinics between 2012 and 2016. Patients underwent genetic assessment and testing according to clinical standards. Chi-squared test was used for phenotypic comparisons. Multivariate logistic regression analysis was performed to determine which phenotypic features were predictive of genetic diagnosis types. RESULTS: Overall, 45.7% of patients in the total cohort were diagnosed with genetic disorders with the vast majority of diagnoses (89.9%) comprising single gene and chromosomal disorders. There were management and treatment implications for almost two-thirds (63.8%) of diagnosed patients. Presence of a single gene disorder or chromosomal diagnosis was predicted by differing combinations of neurological, NDD, and psychiatric phenotypes. CONCLUSION: The results of this study highlight the frequency and impact of genetic diagnosis in psychiatric populations, particularly those with concomitant NDD. Genetic assessment should be considered in psychiatric patients, particularly those with multiple brain phenotypes (psychiatric, neurodevelopmental, neurological).
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Transtornos Mentais , Transtornos do Neurodesenvolvimento , Adulto , Estudos Transversais , Diagnóstico Duplo (Psiquiatria) , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Ontário , FenótipoRESUMO
Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated â¼27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late "catch-up" growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2).
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Anormalidades Múltiplas/genética , Perda Auditiva/genética , Deficiência Intelectual/genética , Disostose Mandibulofacial/genética , Microcefalia/genética , Mutação , Fatores de Alongamento de Peptídeos/genética , Ribonucleoproteína Nuclear Pequena U5/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/patologia , Motivos de Aminoácidos , Bases de Dados Genéticas , Expressão Gênica , Haploinsuficiência , Perda Auditiva/diagnóstico , Perda Auditiva/patologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Disostose Mandibulofacial/diagnóstico , Disostose Mandibulofacial/patologia , Microcefalia/diagnóstico , Microcefalia/patologia , Modelos Moleculares , Dados de Sequência Molecular , Penetrância , Fenótipo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Splicing de RNA , Spliceossomos/genéticaRESUMO
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary connective tissue disorders characterized by joint hypermobility, widespread musculoskeletal pain and tissue fragility. Psychiatric disorders and psychosocial impairment are common, yet poorly characterized, findings in EDS patients. We investigated the frequency and types of psychiatric disorders and their relationship to systemic manifestations in a cohort of 106 classic and hypermobility type EDS patients. In this retrospective study, extensive medical chart review was performed for patients referred at two genetics clinics who were diagnosed with EDS. Statistical analysis was undertaken to determine the frequency of psychiatric disorders and association with systemic findings. Psychiatric disorders were found in 42.5% of the EDS cohort, with 22.7% of patients affected with 2 or more psychiatric diagnoses. Anxiety and depression were most commonly reported, with frequencies of 23.6 and 25.5%, respectively. A variety of other psychiatric diagnoses were also identified. Abdominal pain [odds ratio (OR) 7.38], neuropathic pain (OR 4.07), migraines (OR 5.21), joint pain (OR 2.85) and fatigue (OR 5.55) were significantly associated with the presence of a psychiatric disorder. The presence of any pain symptom was significantly associated with having a psychiatric disorder (OR 9.68). Muscle pain (OR 2.79), abdominal pain (OR 5.78), neuropathic pain (OR 3.91), migraines (OR 2.63) and fatigue (OR 3.78) were significantly associated with having an anxiety or mood disorder. Joint hypermobility and the classic dermatological features of EDS showed no significant association with having a psychiatric disorder. Our findings demonstrate a high frequency of psychiatric disorders and an association with pain symptoms in EDS.
Assuntos
Dor Abdominal/epidemiologia , Artralgia/epidemiologia , Síndrome de Ehlers-Danlos/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Neuralgia/epidemiologia , Dor Abdominal/diagnóstico , Dor Abdominal/psicologia , Adulto , Artralgia/diagnóstico , Artralgia/psicologia , Comorbidade , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/psicologia , Neuralgia/diagnóstico , Neuralgia/psicologia , Razão de Chances , Ontário/epidemiologia , Medição da Dor , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Recurrent 15q13.3 deletions are enriched in multiple neurodevelopmental conditions including intellectual disability, autism, epilepsy, and schizophrenia. However, the 15q13.3 microdeletion syndrome remains ill-defined. METHODS: We systematically compiled all cases of 15q13.3 deletion published before 2014. We also examined three locally available cohorts to identify new adults with 15q13.3 deletions. RESULTS: We identified a total of 246 cases (133 children, 113 adults) with deletions overlapping or within the 15q13.3 (breakpoint (BP)4-BP5) region, including seven novel adult cases from local cohorts. No BP4-BP5 deletions were identified in 23,838 adult controls. Where known, 15q13.3 deletions were typically inherited (85.4%) and disproportionately of maternal origin (P < 0.0001). Overall, 198 cases (121 children, 77 adults; 80.5%) had at least one neuropsychiatric diagnosis. Accounting for ascertainment, developmental disability/intellectual disability was present in 57.7%, epilepsy/seizures in 28.0%, speech problems in 15.9%, autism spectrum disorder in 10.9%, schizophrenia in 10.2%, mood disorder in 10.2%, and attention deficit hyperactivity disorder in 6.5%. By contrast, major congenital malformations, including congenital heart disease (2.4%), were uncommon. Placenta previa occurred in the pregnancies of four cases. CONCLUSION: The 15q13.3 microdeletion syndrome is predominantly characterized by neuropsychiatric expression. There are implications for pre- and postnatal detection, genetic counseling, and anticipatory care.
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Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/etiologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia , Fenótipo , Convulsões/diagnóstico , Convulsões/etiologia , Adulto , Idoso , Pontos de Quebra do Cromossomo , Deleção Cromossômica , Transtornos Cromossômicos/epidemiologia , Cromossomos Humanos Par 15 , Estudos de Coortes , Feminino , Estudos de Associação Genética , Homozigoto , Humanos , Padrões de Herança , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Placenta Prévia , Gravidez , Prevalência , Convulsões/epidemiologiaRESUMO
22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med 17 8, 599-609.
Assuntos
Síndrome de DiGeorge/terapia , Adulto , Deleção Cromossômica , Cromossomos Humanos Par 22 , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Feminino , Testes Genéticos , Humanos , Masculino , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: To investigate the ability of a new clinical model to improve accessibility and expedite the pathway to molecular diagnosis for patients with suspected inherited retinal diseases (IRD). DESIGN: Retrospective cohort study of electronic patient records. PARTICIPANTS: All patients referred to general medical genetic clinic between September 2017 to September 2019 and an ophthalmologist-led IRD clinic between October 2021 to July 2023 for suspected IRD were included. METHODS: The difference in timeliness and accessibility to diagnosis and genetics testing for patients referred for suspected IRDs were compared based on whether they were referred to general medical genetics clinic or an ophthalmologist-led IRD clinic. MAIN OUTCOME MEASURES: The primary outcomes were time to consult from referral; time from initial consult to molecular diagnosis; and the time from initial consult to genetics result disclosure and counseling. Secondary outcomes included number of prior providers investigating the chief complaint; the proportion of patients undergoing genetics testing; and the range of diagnostic investigations undertaken. RESULTS: 473 patients were included, with 212 cases from general medical genetics clinic and 261 from medical retina clinic. The mean time from referral to initial consult was 14 months (±3.33 months) and 4 months (±3.4 months) for general medical genetics and the ophthalmologist-led IRD clinic respectively. The mean time from initial consult to genetics disclosure and counselling was 6 months (±3.6 months) and 3.5 months (±1.8 months) for medical genetics and the ophthalmologist-led model respectively. The total time from initial referral to genetics disclosure and counselling for the medical geneticist-led clinic model was 20-24 months. The total time from initial referral to genetics disclosure and counselling for ophthalmologist-led retinal clinic was 5-8 months. The average number of prior providers seen prior to presenting to ophthalmologist-led retina clinic was 2.05 (range 1-10). CONCLUSIONS: Shifting from the traditional medical genetics model to the new ophthalmologist-led IRD clinical model may improve accessibility and expedite the pathway to molecular diagnosis and subsequent gene therapy trials for patients with suspected IRDs.
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Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50-deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function.
Assuntos
Transtornos do Neurodesenvolvimento , Spliceossomos , Humanos , Spliceossomos/genética , Redes Reguladoras de Genes , Transtornos do Neurodesenvolvimento/genética , Mutação de Sentido Incorreto , Splicing de RNA , Fatores de Processamento de RNA/genética , Proteínas Nucleares/genética , Enzimas Reparadoras do DNA/genéticaRESUMO
We have developed PhenoTips: open source software for collecting and analyzing phenotypic information for patients with genetic disorders. Our software combines an easy-to-use interface, compatible with any device that runs a Web browser, with a standardized database back end. The PhenoTips' user interface closely mirrors clinician workflows so as to facilitate the recording of observations made during the patient encounter. Collected data include demographics, medical history, family history, physical and laboratory measurements, physical findings, and additional notes. Phenotypic information is represented using the Human Phenotype Ontology; however, the complexity of the ontology is hidden behind a user interface, which combines simple selection of common phenotypes with error-tolerant, predictive search of the entire ontology. PhenoTips supports accurate diagnosis by analyzing the entered data, then suggesting additional clinical investigations and providing Online Mendelian Inheritance in Man (OMIM) links to likely disorders. By collecting, classifying, and analyzing phenotypic information during the patient encounter, PhenoTips allows for streamlining of clinic workflow, efficient data entry, improved diagnosis, standardization of collected patient phenotypes, and sharing of anonymized patient phenotype data for the study of rare disorders. Our source code and a demo version of PhenoTips are available at http://phenotips.org.
Assuntos
Bases de Dados Genéticas , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Pesquisa em Genética , Fenótipo , Software , Interface Usuário-Computador , Algoritmos , Criança , Sistemas de Gerenciamento de Base de Dados , Bases de Dados Factuais , Ontologia Genética , Humanos , Armazenamento e Recuperação da InformaçãoRESUMO
The GENCOV study aims to identify patient factors which affect COVID-19 severity and outcomes. Here, we aimed to evaluate patient characteristics, acute symptoms and their persistence, and associations with hospitalization. Participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Patient-reported demographics, medical history, and COVID-19 symptoms and complications were collected through an intake survey. Regression analyses were performed to identify associations with outcomes including hospitalization and COVID-19 symptoms. In total, 966 responses were obtained from 1106 eligible participants (87% response rate) between November 2020 and May 2022. Increasing continuous age (aOR: 1.05 [95%CI: 1.01-1.08]) and BMI (aOR: 1.17 [95%CI: 1.10-1.24]), non-White/European ethnicity (aOR: 2.72 [95%CI: 1.22-6.05]), hypertension (aOR: 2.78 [95%CI: 1.22-6.34]), and infection by viral variants (aOR: 5.43 [95%CI: 1.45-20.34]) were identified as risk factors for hospitalization. Several symptoms including shortness of breath and fever were found to be more common among inpatients and tended to persist for longer durations following acute illness. Sex, age, ethnicity, BMI, vaccination status, viral strain, and underlying health conditions were associated with developing and having persistent symptoms. By improving our understanding of risk factors for severe COVID-19, our findings may guide COVID-19 patient management strategies by enabling more efficient clinical decision making.
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COVID-19 , Humanos , COVID-19/epidemiologia , Hospitalização , Pacientes Internados , Ontário/epidemiologia , Fatores de RiscoRESUMO
Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.