The role of protective genetic variants in modulating epigenetic aging.

Several progeroid syndromes' causative mutations have been linked to epigenetic age acceleration as measured via several epigenetic clocks. At the same time, several protective variants have also been discovered that can reduce the risk of developing certain age-related disorders. However, the impact of these protective variants on epigenetic aging has not been well elucidated.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Cardiac autonomic neuropathy: impact on severe hypoglycemic unawareness and orthostatic hypotension in diabetic dysautonomia, a case series and review.

Diabetic autonomic neuropathy (DAN) and its associated cardiovascular autonomic neuropathy (CAN) can lead to potentially fatal complications. We analyzed two distinct cases of DAN/CAN based on comprehensive cardiovascular autonomic reflex tests (CARTs). Case 1 involves a 27-year-old patient with T1DM suffering from recurrent severe hypoglycemic unawareness due to DAN.

Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents.

Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery: a multi-ancestry study in 10 960 individuals from 9 biobanks.

Obesity is a significant public health concern. GLP-1 receptor agonists (GLP1-RA), predominantly in use as a type 2 diabetes treatment, are a promising pharmacological approach for weight loss, while bariatric surgery (BS) remains a durable, but invasive, intervention. Despite observed heterogeneity in weight loss effects, the genetic effects on weight loss from GLP1-RA and BS have not been extensively explored in large sample sizes, and most studies have focused on differences in race and ethnicity, rather than genetic ancestry.

Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants.

Arabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation in 14,392 whole genomes from the Qatar Genome Program (QGP) across the list of 78 actionable genes (v3.1) determined by the American College of Medical Genetics and Genomics (ACMG).

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.

Qatar genome: Insights on genomics from the Middle East.

Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is underrepresented in the human genome variation databases. Here we describe insights from Phase 1 of the Qatar Genome Program with whole genome sequenced 6047 individuals from Qatar. We identified more than 88 million variants of which 24 million are novel and 23 million are singletons.

One Year of SARS-CoV-2: Genomic Characterization of COVID-19 Outbreak in Qatar.

Qatar, a country with a strong health system and a diverse population consisting mainly of expatriate residents, has experienced two large waves of COVID-19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period.

Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations.

Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate.

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks.

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks.

Improving Bioinformatics Prediction of microRNA Targets by Ranks Aggregation.

microRNAs are noncoding RNAs which downregulate a large number of target mRNAs and modulate cell activity. Despite continued progress, bioinformatics prediction of microRNA targets remains a challenge since available software still suffer from a lack of accuracy and sensitivity. Moreover, these tools show fairly inconsistent results from one another.

DiNAMO: highly sensitive DNA motif discovery in high-throughput sequencing data.

Background: Discovering over-represented approximate motifs in DNA sequences is an essential part of bioinformatics. This topic has been studied extensively because of the increasing number of potential applications. However, it remains a difficult challenge, especially with the huge quantity of data generated by high throughput sequencing technologies.

Awareness and Knowledge Among Internal Medicine Resident Trainees for Dose Adjustment of Analgesics and Neuropsychotropic Medications in CKD.

Objectives: Errors in drug dosing lead to poor patient outcomes and are common in patients with chronic kidney disease (CKD). Because the majority of patients with CKD are being treated by physicians specializing in internal medicine, we studied the awareness and knowledge that internal medicine resident trainees (IMRTs) have regarding the correct dosage of commonly used analgesic and neuropsychotropic medications for patients with CKD.

Methods: We surveyed 353 IMRTs about their awareness of whether a medication needs dose adjustment in patients with CKD and knowledge for medication adjustment by level of glomerular filtration rate.

Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

Background: Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients.

Methods: We studied 192 MM patients that underwent ASCT.