Publications

CONCLUSION: Preinjury characteristics, such as psychiatric history and unemployment, and injury characteristics, such as violent injury cause, can increase the risk of mental health problems after TBI. The identification of patients at risk should be guided by early screening of mental health.

Genetic summary data are broadly accessible and highly useful, including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into summary data, such as allele frequencies, masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted-for substructure limits summary data usability, especially for understudied or admixed populations. There is a need for […]

CONCLUSIONS: Analyses of large-scale population cohorts such as the UKB can be a critical tool to further our understanding of rare diseases in general. Continued research in this area could lead to more precise diagnostics and personalized treatment strategies for patients with rare and undiagnosed conditions.

Diabetes is a leading cause of global mortality and disability, and its economic burden is substantial. This Review focuses on type 2 diabetes, which makes up 90-95% of all diabetes cases. Type 2 diabetes involves a progressive loss of insulin secretion often alongside insulin resistance and metabolic syndrome. Although obesity and a sedentary lifestyle are considerable contributors, research over the last 25 years has shown that type 2 diabetes develops on a predisposing genetic background,...

CONCLUSIONS AND RELEVANCE: In this cohort study, LDL-C and T2D risks were inversely associated across genetic mechanisms for LDL-C variation. Further elucidation of the mechanisms associating low LDL-C risk with increased risk of T2D is warranted.

OBJECTIVES: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset.

CONCLUSION: Despite treatment, EPC typically lasts at least hours, and often days or longer. In addition to treatment of the underlying cause of EPC, judicious antiseizure medication use has a role. However, care should be taken not to cause harm (such as respiratory depression) with antiseizure medications, particularly noting that seizures are likely to be prolonged irrespective of antiseizure medication choice.

In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory,...

CONCLUSIONS: We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within or near that gene. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function. We present a transcriptomics-first method to diagnose individuals with rare diseases by examining transcriptome-wide...

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The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results. The latent space ECG model identified associations with 645 prevalent and 606 incident Phecodes....

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the...

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium...

PURPOSE OF REVIEW: The human circadian system regulates several physiological processes, including metabolism, which becomes significantly disrupted during critical illness. The common use of 24-h continuous nutrition support feeding in the intensive care unit (ICU) may further exacerbate these disruptions; this review evaluates recent evidence comparing continuous and intermittent feeding schedules in critically ill adults.

CONCLUSIONS AND RELEVANCE: In this survey study of 42 597 US adults, irritability represented another correlate of social media use that merits further characterization, in light of known associations with depression and suicidality.

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Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by...

CONCLUSION: mtDNA variant calling from data generated by exome and genome sequencing for nuclear variant analysis resulted in a genetic diagnosis or detection of a candidate variant for 0.4% of undiagnosed families affected by a broad range of rare diseases.

Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to...

CONCLUSIONS: With a causally informed strategy, we demonstrated the potential effects of numerous hypothetical interventions on modifiable factors for depression risk reduction, across multiple preventive settings. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

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In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using local ancestry inference (LAI). Accurate LAI is crucial to ensure that downstream analyses accurately reflect the genetic ancestry of research participants. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries-African (AFR), Amerindigenous (AMR), and...

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Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, their 943 unaffected parents, and 6665 adult controls. We discovered a sex-biased association between very large (>1 megabase) germline chromosomal abnormalities and increased risk of solid tumors in male children. The overall impact of […]

Participation in leisure and social activities (LSA) is associated with better health outcomes and lower mortality^(1-3). Previous observational studies demonstrated a relationship between engagement in LSA and both mental and physical health^(4,5). Although several studies⁶ examined the association between LSA and health outcomes, including cardiovascular disease, their possible causal relationship has not been studied. In this study, we investigated the causal relationship between LSA and...

Kleefstra syndrome (KLEFS) is a genetic neurodevelopmental disorder caused by haploinsufficiency of EHMT1. The full spectrum of clinical features and genotype-phenotype correlations is currently not fully understood. We performed a retrospective chart review of patients with KLEFS evaluated at the Boston Children's Hospital Kleefstra Clinic. There were 65 individuals (40 females, 25 males, mean age 9.3 years). 17% had large 9q34 deletions (≥ 1 Mb), 29% had small 9q34 deletions (

Practices for controlling intracranial pressure (ICP) in traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) vary considerably between centres. To help understand the rational basis for such variance in care, this study aims to identify the patient-level predictors of changes in ICP management. We extracted all heterogeneous data (2008 pre-ICU and ICU variables) collected from a prospective cohort (n = 844, 51 ICUs) of ICP-monitored TBI patients in the […]

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD,...

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There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, modifying version after version into shape. Acknowledging these biases, here are the 2024 articles that we think...

Down syndrome is a chromosomal condition occurring in about 220,000 individuals in the United States. Previous research showed almost 1 in 5 individuals with Down syndrome in the U.S. face significant geographic obstacles to receiving specialty care. The purpose of this study was to extend this work and learn more about socioeconomic barriers to Down syndrome specialty clinics. We quantified the percentage of the general population in each U.S. state living within a 2-hour drive of a Down...

CONCLUSION: This work highlights the importance of considering methodological decision points in interpreting the impact of PRS on prediction performance in clinical models.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of […]

CONCLUSION: Findings can inform more effective notification and testing practices for families of newborns at risk for hereditary genetic conditions.

CONCLUSION: We identified six anterior uveitis-associated loci, including three novel loci with genome-wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune-related disorders, providing a foundation for further research and potential therapeutic interventions.

CONCLUSIONS: In addition to CAA burden and patient location 1-week post-ICH, social vulnerability was independently associated with depression among ICH survivors. Our findings suggest that social vulnerability influences ICH outcomes. Future studies should investigate how poststroke clinical care interventions can address SDOH effects to reduce incident depression and improve outcomes among ICH survivors.

BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the […]

OBJECTIVE: Night eating syndrome (NES) is an eating disorder characterized by evening hyperphagia. Despite having a prevalence comparable to some other eating disorders, NES remains sparsely investigated and poorly characterized. The present study examined the phenotypic and genetic associations for NES in the clinical Mass General Brigham Biobank.

MOTIVATION: The Variant Call Format (VCF) is widely used in genome sequencing but scales poorly. For instance, we estimate a 150,000 genome VCF would occupy 900 TiB, making it costly and complicated to produce, analyze, and store. The issue stems from VCF's requirement to densely represent both reference-genotypes and allele-indexed arrays. These requirements lead to unnecessary data duplication and, ultimately, very large files.

OBJECTIVE: In this cross-sectional study, we aim to investigate the interactions between obesity, siesta behavior, and the genetic propensity for siesta in a Mediterranean population, in whom siesta is deeply rooted.

Variably protease-sensitive prionopathy (VPSPr) is a rare, atypical subtype of prion disease in which many patients exhibit a family history of dementia. Rare protein-coding variants in PRNP, which are causal for all known forms of genetic prion disease, have been ruled out in all VPSPr cases to date, leading to suspicion that VPSPr could be caused by variants in other genes or by non-coding variation in or near PRNP. We performed exome sequencing and targeted sequencing of PRNP non-coding...

Congenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described for ALG10 , encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP...

CONCLUSIONS: When resources are limited, interventions should prioritise individuals with high stress reactivity who have experienced multiple stressful life events, as these individuals may be at greater risk for depression.

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CONCLUSION: Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.

CONCLUSIONS: The T2D polygenic score serves as an independent predictor of incident diabetes, particularly among individuals with lower distribution of traditional risk factors.

CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to...

Genetic mutations that yield defective cystic fibrosis transmembrane regulator (CFTR) protein cause cystic fibrosis, a life-limiting autosomal recessive Mendelian disorder. A protective role of CFTR loss-of-function mutations in inflammatory bowel disease (IBD) has been suggested, but its evidence has been inconclusive and contradictory. Here, leveraging the largest IBD exome sequencing dataset to date, comprising 38,558 cases and 66,945 controls in the discovery stage, and 35,797 cases and...

Ultraviolet (UV) radiation is known to be the most important environmental carcinogen for cutaneous melanoma. While genomic analyses of melanoma tumors implicate a high rate of UV damage, the experimental induction and recovery of bona fide UV-signature changes have not been directly observed. To replicate recurrent UV mutations from TCGA_SKCM specimens, we UV-irradiated cultured immortalized human melanocytes and subjected them to in vivo tumorigenesis assays. Exome sequencing of the...

CONCLUSION: The ARID1B spectrum is broad, and as patients age, there is a significant shift in the medical aspects requiring attention. To address the changing medical needs with increasing age, we have formulated recommendations to promote timely intervention in an attempt to mitigate disease progression.

CONCLUSION: Our extensive evaluation of SMA Finder on exome, genome and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, as well as the existence of treatment options, we propose that it is time to add SMN1 to the ACMG list of genes […]

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The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals^(1,2), undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics^(3,4). Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints⁵, and...

INTRODUCTION/AIMS: Hereditary transthyretin amyloidosis (ATTRv) is a genetic condition caused by pathogenic variants in the transthyretin (TTR) gene resulting in multisystem amyloid deposition, especially in peripheral nerve and heart. Information on the prevalence of ATTRv in the United States is limited. The objective of this study was to understand the prevalence and genetic ancestry in the Val142Ile population in a large regional US population.

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CONCLUSIONS: Our EWAS on early DKD progression identified a podocyte-specific CDKN1C locus. EWAS on late progression proposed novel CpGs for ESKD risk and confirmed previously known sites for kidney function. Since DNA methylation signals could improve disease course prediction, a combination of blood-derived methylation sites could serve as a potential prognostic biomarker.

Familial dysautonomia (FD) is a fatal autosomal recessive congenital neuropathy caused by a T-to-C mutation in intron 20 of the Elongator acetyltransferase complex subunit 1 (ELP1) gene, which causes tissue-specific skipping of exon 20 and reduction of ELP1 protein. Here, we developed a base editor (BE) approach to precisely correct this mutation. By optimizing Cas9 variants and screening multiple gRNAs, we identified a combination that was able to promote up to 70% on-target editing in […]

CONCLUSIONS: Our findings reveal pleiotropic genetic factors influencing chronotype and ease of getting-up, emphasizing GPR61 's rs12044778 and nearby genes like AMIGO1 and ATXN7L2 . These insights advance understanding of circadian preferences and suggest potential therapeutic interventions.

KIF21A encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant in KIF21A p.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts. She presented with...

CONCLUSION: Elevated Lp(a) is associated with an increased risk of MACE independent of hs-CRP levels in both primary and secondary prevention populations.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait […]

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The human genome is packaged within a three-dimensional (3D) nucleus and organized into structural units known as compartments, topologically associating domains (TADs), and loops. TAD boundaries, separating adjacent TADs, have been found to be well conserved across mammalian species and more evolutionarily constrained than TADs themselves. Recent studies show that structural variants (SVs) can modify 3D genomes through the disruption of TADs, which play an essential role in insulating genes...

Alzheimer's disease (AD) is associated with memory and cognitive impairment caused by progressive degeneration of neurons. The events leading to neuronal death are associated with the accumulation of aggregating proteins in neurons and glia of the affected brain regions, in particular extracellular deposition of amyloid plaques and intracellular formation of tau neurofibrillary tangles. Moreover, the accumulation of pathological tau proteoforms in the brain concurring with disease progression […]

Canavan disease (CD) is an ultra-rare autosomal recessive leukodystrophy caused by loss-of-function mutations in ASPA, which encodes aspartoacylase (ASPA), leading to accumulation of N-acetylaspartate (NAA). Patients with CD typically present with profound psychomotor deficits within the first 6 months of life and meet few motor milestones. Within CD a subset of patients exhibits a milder phenotype with more milestone acquisition, possibly related to greater residual ASPA activity. An ongoing […]

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, […]

CONCLUSIONS: Our findings link TRPML-1 dysfunction to the development of kidney disease in MLIV, providing new insights into its pathogenesis and potential therapeutic targets.

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Portable, low-field magnetic resonance imaging (LF-MRI) of the brain may facilitate point-of-care assessment of patients with Alzheimer's disease (AD) in settings where conventional MRI cannot. However, image quality is limited by a lower signal-to-noise ratio. Here, we optimize LF-MRI acquisition and develop a freely available machine learning pipeline to quantify brain morphometry and white matter hyperintensities (WMH). We validate the pipeline and apply it to outpatients presenting with […]

Multidimensional host and viral factors determine the clinical course of COVID-19. While the virology of the disease is well studied, investigating host-related factors, including genome, transcriptome, metabolome, and exposome, can provide valuable insights into the underlying pathophysiology. We conducted integrative omics analyses to explore their intricate interplay in COVID-19. We used data from the UK Biobank (UKB), and employed single-omics, pairwise-omics, and multi-omics models to...

CONCLUSIONS: When compared with other clinical risk factors, PGS was the strongest predictor of event recurrence among patients with an early-onset MI. Though the discriminative power of recurrent event prediction in this cohort was modest, the addition of PGS significantly improved discrimination.

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, […]

Genetic vascular disorders are prevalent diseases that have diverse etiologies and few treatment options. Pathogenic missense mutations in the alpha actin isotype 2 gene (ACTA2) primarily affect smooth muscle cell (SMC) function and cause multisystemic smooth muscle dysfunction syndrome (MSMDS), a genetic vasculopathy that is associated with stroke, aortic dissection, and death in childhood. Here, we explored genome editing to correct the most common MSMDS-causative mutation ACTA2 R179H. In a...

Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH, two of these are […]

CONCLUSION: Given that forthcoming professional guidance in variant classification will advise the use of VUS subclasses, the experience of our laboratories in using VUS subclasses can inform future practices.

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CONCLUSION: The SD-GCEP addresses a critical gap in gene curation efforts, enabling inclusion of genes for syndromic disorders in clinical testing and contributing to keeping pace with the rapid discovery of new genetic syndromes.

Using quality improvement methods, we aimed to implement a protocol to assess for dementia among adults with Down syndrome (DS). To track implementation, interval retrospective chart review of patients with DS with visits to the Massachusetts General Hospital DS Program (MGH DSP) was conducted quarterly. The impact of a newly implemented protocol created and informed by clinical experts in the MGH DSP including laboratory tests, imaging, referrals, and screening tools for dementia and mental...

CONCLUSION AND RELEVANCE: Tenecteplase and alteplase had comparable DTN times for treatment of AIS and similar safety endpoints. Further studies are warranted to identify opportunities to streamline DTN times with tenecteplase.

[This corrects the article DOI: 10.3389/fpsyt.2024.1373797.].

PURPOSE OF REVIEW: This review highlights contributions of the Global Lipids Genetics Consortium (GLGC) in advancing the understanding of the genetic etiology of blood lipid traits, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL cholesterol. We emphasize the consortium's collaborative efforts, discoveries related to lipid and lipoprotein biology, methodological advancements, and utilization in areas extending beyond lipid research.

Brentuximab vedotin is a combination monoclonal antibody to anti-CD30 conjugated to the anti-tubulin agent monomethyl auristatin E. It is approved for the treatment of mycosis fungoides, Hodgkin's lymphoma, and systemic anaplastic large cell lymphoma. Brentuximab has been associated with a number of potential adverse reactions; however, reports of renal complications are rare. A 73-year-old male with mycosis fungoides was admitted to hospital with acute kidney injury following his third cycle […]

DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers-especially those with longitudinal...

CONCLUSIONS: Metabolically stable HPN adult consumers have 24-h glucose measures comparable to healthy adults yet are notable for more time spent below range. The glucose profiles are influenced by HPN parameters such as tapering and dextrose and behaviors including smoking, depressive symptoms, and insomnia.

Huntington's disease (HD) arises from a CAG expansion in the huntingtin (HTT) gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant HTT mRNA (mHTT) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in HTT's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset....

Obstructive sleep apnea (OSA) is a multifactorial sleep disorder characterized by a strong genetic basis. Excessive daytime sleepiness (EDS) is a symptom that is reported by a subset of OSA patients, persisting even after treatment with continuous positive airway pressure (CPAP). It is recognized as a clinical subtype underlying OSA carrying alarming heightened cardiovascular risk. Thus, conceptualizing EDS as an exposure variable, we sought to investigate EDS's influence on genetic variation...

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BACKGROUND: No treatment is available to prevent brain oedema, which can occur after a large hemispheric infarction. Glibenclamide has previously been shown to improve functional outcome and reduce neurological or oedema-related death in patients younger than 70 years who were at risk of brain oedema after an acute ischaemic stroke. We aimed to assess whether intravenous glibenclamide could improve functional outcome at 90 days in patients with large hemispheric infarction.

Early identification of high-risk individuals through the analysis of their unique disease trajectories has a strong potential to support efficient prevention and clinical management across a range of chronic conditions. In this paper we present a novel approach for dynamic modeling of the evolution of chronic disease risks over time, incorporating individual genetic predispositions. Our approach uses a hierarchical Bayesian topic model including Gaussian Processes to capture age effects. It...

Cardiac diseases represent common highly morbid conditions for which molecular mechanisms remain incompletely understood. Here we report the analysis of 1,459 protein measurements in 44,313 UK Biobank participants to characterize the circulating proteome associated with incident coronary artery disease, heart failure, atrial fibrillation and aortic stenosis. Multivariable-adjusted Cox regression identified 820 protein-disease associations-including 441 proteins-at Bonferroni-adjusted P

Dilated cardiomyopathy (DCM) is a heart muscle disease that represents an important cause of morbidity and mortality, yet causal mechanisms remain largely elusive. Here, we perform a large-scale genome-wide association study and multitrait analysis for DCM using 9,365 cases and 946,368 controls. We identify 70 genome-wide significant loci, which show broad replication in independent samples and map to 63 prioritized genes. Tissue, cell type and pathway enrichment analyses highlight the […]

[This corrects the article DOI: 10.3389/fneur.2023.1291020.].

Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder. Our recessive analysis identified […]

Although rare neurodevelopmental conditions have a large Mendelian component¹, common genetic variants also contribute to risk^(2,3). However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family […]