medRxiv : the preprint server for health sciences最新文献

{"title":"Imprecision nutrition? Duplicate meals result in unreliable individual glycemic responses measured by continuous glucose monitors across four dietary patterns in adults without diabetes.","authors":"Aaron Hengist, Jude Anthony Ong, Katherine McNeel, Juen Guo, Kevin D Hall","doi":"10.1101/2023.06.14.23291406","DOIUrl":"10.1101/2023.06.14.23291406","url":null,"abstract":"<p><strong>Background: </strong>Continuous glucose monitors (CGMs) are being used to characterize postprandial glycemic responses and thereby provide personalized dietary advice to minimize glycemic excursions. However, the efficacy of such advice depends on reliable CGM responses.</p><p><strong>Objective: </strong>To explore within-subject variability of CGM responses to duplicate meals in an inpatient setting.</p><p><strong>Methods: </strong>CGM data were collected in two controlled feeding studies (NCT03407053 and NCT03878108) in 30 participants without diabetes capturing 1056 meal responses in duplicate ~1 week apart from four dietary patterns. One study used two different CGMs (Abbott Freestyle Libre Pro and Dexcom G4 Platinum) whereas the other study used only Dexcom. We calculated the incremental area under the curve (iAUC) for each 2-h post-meal period and compared within-subject iAUCs using the same CGM for the duplicate meals using linear correlations, intra-class correlation coefficients (ICC), Bland-Altman analyses, and compared individual variability of glycemic responses to duplicate meals versus different meals using standard deviations (SDs).</p><p><strong>Results: </strong>There were weak to moderate positive linear correlations between within- subject iAUCs for duplicate meals (Abbott r=0.47, p<0.0001, Dexcom r=0.43, p<0.0001), with low within-participant reliability indicated by ICC (Abbott 0.31, Dexcom 0.14). Bland-Altman analyses indicated wide limits of agreement (Abbott -31.3 to 31.5 mg/dL, Dexcom -30.8 to 30.4 mg/dL) but no significant bias of mean iAUCs for duplicate meals (Abbott 0.1 mg/dL, Dexcom -0.2 mg/dL). Individual variability of glycemic responses to duplicate meals was similar to that of different meals evaluated each diet week for both Abbott (SD_duplicate = 10.7 mg/dL , SD_{week 1} =12.4 mg/dL, SD_{week 2} =11.6 mg/dL, <i>p</i>=0.38) and Dexcom (SD_duplicate = 11.1 mg/dL, SD_{week 1} = 11.5 mg/dL, SD_{week 2} =11.9 mg/dL, <i>p</i>=0.60).</p><p><strong>Conclusions: </strong>Individual postprandial CGM responses to duplicate meals were unreliable in adults without diabetes. Personalized diet advice based on CGM measurements in adults without diabetes requires more reliable methods involving aggregated repeated measurements.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corpus callosum abnormalities at term-equivalent age are associated with language development at two years corrected age in infants born very preterm.","authors":"Katsuaki Kojima, Julia E Kline, Mekibib Altaye, Beth M Kline-Fath, Nehal A Parikh","doi":"10.1101/2023.09.20.23295848","DOIUrl":"10.1101/2023.09.20.23295848","url":null,"abstract":"<p><p>We studied the impact of microstructural abnormalities in the corpus callosum on language development in 348 infants born very prematurely. We discovered that the fractional anisotropy of the corpus callosum anterior midbody was a significant predictor of standardized language scores at two years, independent of clinical and social risk factors.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/bd/nihpp-2023.09.20.23295848v1.PMC10543245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.","authors":"Danyang Li, Oliver Pain, Chiara Fabbri, Win Lee Edwin Wong, Chris Wai Hang Lo, Stephan Ripke, Annamaria Cattaneo, Daniel Souery, Mojca Z Dernovsek, Neven Henigsberg, Joanna Hauser, Glyn Lewis, Ole Mors, Nader Perroud, Marcella Rietschel, Rudolf Uher, Wolfgang Maier, Bernhard T Baune, Joanna M Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Richard Weinshilboum, Andrew M McIntosh, Cathryn M Lewis","doi":"10.1101/2023.06.26.23291890","DOIUrl":"10.1101/2023.06.26.23291890","url":null,"abstract":"<p><p>Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. The association of CYP2C19 and CYP2D6 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR=1.46, 95% CI [1.03, 2.06], p=0.033, heterogeneity I²=0%, subgroup difference p=0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19 and CYP2D6, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. CYP2D6 structural variants cannot be imputed from genotype data, limiting inference of pharmacogenetic effects. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/5a/nihpp-2023.06.26.23291890v1.PMC10327261.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early underdetected dissemination across countries followed by extensive local transmission propelled the 2022 mpox epidemic.","authors":"Miguel I Paredes, Nashwa Ahmed, Marlin Figgins, Vittoria Colizza, Philippe Lemey, John T McCrone, Nicola Müller, Cécile Tran-Kiem, Trevor Bedford","doi":"10.1101/2023.07.27.23293266","DOIUrl":"10.1101/2023.07.27.23293266","url":null,"abstract":"<p><p>The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case-reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418578/pdf/nihpp-2023.07.27.23293266v2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.","authors":"Amanda Biewer, Christine Tzelios, Karen Tintaya, Betsabe Roman, Shelley Hurwitz, Courtney M Yuen, Carole D Mitnick, Edward Nardell, Leonid Lecca, Dylan B Tierney, Ruvandhi R Nathavitharana","doi":"10.1101/2023.05.17.23290110","DOIUrl":"10.1101/2023.05.17.23290110","url":null,"abstract":"<p><strong>Introduction: </strong>Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy.</p><p><strong>Methods: </strong>We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors.</p><p><strong>Results: </strong>In the triage cohort (n=387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n=191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort.</p><p><strong>Conclusions: </strong>qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous detection and quantification of multiple pathogen targets in wastewater.","authors":"Gouthami Rao, Drew Capone, Kevin Zhu, Abigail Knoble, Yarrow Linden, Ryan Clark, Amanda Lai, Juhee Kim, Ching-Hua Huang, Aaron Bivins, Joe Brown","doi":"10.1101/2023.06.23.23291792","DOIUrl":"10.1101/2023.06.23.23291792","url":null,"abstract":"<p><p>Wastewater-based epidemiology has emerged as a critical tool for public health surveillance, building on decades of environmental surveillance work for pathogens such as poliovirus. Work to date has been limited to monitoring a single pathogen or small numbers of pathogens in targeted studies; however, few studies consider simultaneous quantitative analysis of a wide variety of pathogens, which could greatly increase the utility of wastewater surveillance. We developed a novel quantitative multi-pathogen surveillance approach (35 pathogen targets including bacteria, viruses, protozoa, and helminths) using TaqMan Array Cards (TAC) and applied the method on concentrated wastewater samples collected at four wastewater treatment plants in Atlanta, GA from February to October of 2020. From sewersheds serving approximately 2 million people, we detected a wide range of targets including many we expected to find in wastewater (e.g., enterotoxigenic <i>E. coli</i> and <i>Giardia</i> in 97% of 29 samples at stable concentrations) as well as unexpected targets including <i>Strongyloides stercoralis</i> (a human threadworm rarely observed in the USA). Other notable detections included SARS-CoV-2, but also several pathogen targets that are not commonly included in wastewater surveillance like <i>Acanthamoeba</i> spp., <i>Balantidium coli, Entamoeba histolytica</i>, astrovirus, norovirus, and sapovirus. Our data suggest broad utility in expanding the scope of enteric pathogen surveillance in wastewaters, with potential for application in a variety of settings where pathogen quantification in fecal waste streams can inform public health surveillance and selection of control measures to limit infections.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Phenotyping for Atopic Dermatitis with Transformers and Machine Learning.","authors":"Andrew Wang, Rachel Fulton, Sy Hwang, David J Margolis, Danielle L Mowery","doi":"10.1101/2023.08.25.23294636","DOIUrl":"10.1101/2023.08.25.23294636","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic skin condition that millions of people around the world live with each day. Performing research studies into identifying the causes and treatment for this disease has great potential to provide benefit for these individuals. However, AD clinical trial recruitment is a non-trivial task due to variance in diagnostic precision and phenotypic definitions leveraged by different clinicians as well as time spent finding, recruiting, and enrolling patients by clinicians to become study subjects. Thus, there is a need for automatic and effective patient phenotyping for cohort recruitment.</p><p><strong>Objective: </strong>Our study aims to present an approach for identifying patients whose electronic health records suggest that they may have AD.</p><p><strong>Methods: </strong>We created a vectorized representation of each patient and trained various supervised machine learning methods to classify when a patient has AD. Each patient is represented by a vector of either probabilities or binary values where each value indicates whether they meet a different criteria for AD diagnosis.</p><p><strong>Results: </strong>The most accurate AD classifier performed with a class-balanced accuracy of 0.8036, a precision of 0.8400, and a recall of 0.7500 when using XGBoost (Extreme Gradient Boosting).</p><p><strong>Conclusions: </strong>Creating an automated approach for identifying patient cohorts has the potential to accelerate, standardize, and automate the process of patient recruitment for AD studies; therefore, reducing clinician burden and informing knowledge discovery of better treatment options for AD.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neurophysiological brain-fingerprint of Parkinson's disease.","authors":"Jason da Silva Castanheira, Alex I Wiesman, Justine Y Hansen, Bratislav Misic, Sylvain Baillet","doi":"10.1101/2023.02.03.23285441","DOIUrl":"10.1101/2023.02.03.23285441","url":null,"abstract":"<p><p>In this study, we investigate the clinical potential of brain-fingerprints derived from electrophysiological brain activity for diagnostics and progression monitoring of Parkinson's disease (PD). We obtained brain-fingerprints from PD patients and age-matched healthy controls using short, task-free magnetoencephalographic recordings. The rhythmic components of the individual brain-fingerprint distinguished between patients and healthy participants with approximately 90% accuracy. The most prominent cortical features of the Parkinson's brain-fingerprint mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also show that Parkinson's disease stages can be decoded directly from cortical neurophysiological activity. Additionally, our study reveals that the cortical topography of the Parkinson's brain-fingerprint aligns with that of neurotransmitter systems affected by the disease's pathophysiology. We further demonstrate that the arrhythmic components of cortical activity are more variable over short periods of time in patients with Parkinson's disease than in healthy controls, making individual differentiation between patients based on these features more challenging and explaining previous negative published results. Overall, we outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and clinical staging of Parkinson's disease. For this reason, the proposed definition of a rhythmic brain-fingerprint of Parkinson's disease may contribute to novel, refined approaches to patient stratification and to the improved identification and testing of therapeutic neurostimulation targets.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/c3/nihpp-2023.02.03.23285441v1.PMC9934726.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted malaria elimination interventions reduce <i>Plasmodium falciparum</i> infections up to 3 kilometers away.","authors":"Jade Benjamin-Chung, Haodong Li, Anna Nguyen, Gabriella Barratt Heitmann, Adam Bennett, Henry Ntuku, Lisa M Prach, Munyaradzi Tambo, Lindsey Wu, Chris Drakeley, Roly Gosling, Davis Mumbengegwi, Immo Kleinschmidt, Jennifer L Smith, Alan Hubbard, Mark van der Laan, Michelle S Hsiang","doi":"10.1101/2023.09.19.23295806","DOIUrl":"10.1101/2023.09.19.23295806","url":null,"abstract":"<p><p>Malaria elimination interventions in low-transmission settings aim to extinguish hot spots and prevent transmission to nearby areas. In malaria elimination settings, the World Health Organization recommends reactive, focal interventions targeted to the area near malaria cases shortly after they are detected. A key question is whether these interventions reduce transmission to nearby uninfected or asymptomatic individuals who did not receive interventions. Here, we measured direct effects (among intervention recipients) and spillover effects (among non-recipients) of reactive, focal interventions delivered within 500m of confirmed malaria index cases in a cluster-randomized trial in Namibia. The trial delivered malaria chemoprevention (artemether lumefantrine) and vector control (indoor residual spraying with Actellic) separately and in combination using a factorial design. We compared incidence, infection prevalence, and seroprevalence between study arms among intervention recipients (direct effects) and non-recipients (spillover effects) up to 3 km away from index cases. We calculated incremental cost-effectiveness ratios accounting for spillover effects. The combined chemoprevention and vector control intervention produced direct effects and spillover effects. In the primary analysis among non-recipients within 1 km from index cases, the combined intervention reduced malaria incidence by 43% (95% CI 20%, 59%). In secondary analyses among non-recipients 500m-3 km from interventions, the combined intervention reduced infection by 79% (6%, 95%) and seroprevalence 34% (20%, 45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 37%. Our findings provide the first evidence that targeting hot spots with combined chemoprevention and vector control interventions can indirectly benefit non-recipients up to 3 km away.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41104666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Known pathogenic gene variants and new candidates detected in Sudden Unexpected Infant Death using Whole Genome Sequencing.","authors":"Angela M Bard, Lindsay V Clark, Erdal Cosgun, Kimberly A Aldinger, Andrew Timms, Lely A Quina, Juan M Lavista Ferres, David Jardine, Elisabeth A Haas, Tatiana M Becker, Chelsea M Pagan, Avni Santani, Diego Martinez, Soumitra Barua, Zakkary McNutt, Addie Nesbitt, Edwin A Mitchell, Jan-Marino Ramirez","doi":"10.1101/2023.09.11.23295207","DOIUrl":"10.1101/2023.09.11.23295207","url":null,"abstract":"<p><strong>Purpose: </strong>To gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID).</p><p><strong>Methods: </strong>Whole Genome Sequencing (WGS) was performed on 145 infants that succumbed to SUID, and 576 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences.</p><p><strong>Results: </strong>Variants of interest were identified in 86 genes, 63.4% of our cohort. Seventy-one of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria (Figure 1).</p><p><strong>Conclusion: </strong>Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.</p>","PeriodicalId":18659,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}