Genomic Analyses of Major SARS-CoV-2 Variants Predicting Multiple Regions of Pathogenic and Transmissive Importance.

The rapid evolution of SARS-CoV-2 has fueled its global proliferation since its discovery in 2019, with several notable variants having been responsible for increases in cases of coronavirus disease 2019 (COVID-19). Analyses of codon bias and usage in these variants between phylogenetic clades or lineages may grant insights into the evolution of SARS-CoV-2 and identify target codons indicative of evolutionary or mutative trends that may prove useful in tracking or defending oneself against emerging strains. We processed a cohort of 120 SARS-CoV-2 genome sequences through a statistical and bioinformatic pipeline to identify codons presenting evidence of selective pressure as well as codon coevolution. We report the identification of two codon sites in the orf8 and N genes demonstrating such evidence with real-world impacts on pathogenicity and transmissivity.

Complete genome sequences of five Ackermannviridae that infect Enterobacteriaceae hosts.

This announcement contains the whole genome sequences of five Ackermannviridae that infect members of the Enterobacteriaceae family of bacteria. Four of the five phages were isolated using Salmonella enterica serovar Typhimurium as a bacterial host: AR2819, Sajous1, SilasIsHot, and FrontPhageNews. ChubbyThor was isolated using Shigella boydii.

Influence of Admixture on Phenotypes.

Individuals of European descent have historically been the focus of genetic studies and possess relatively homogenous genomes. As a result, analytical methods have been developed and optimized with such genomes in mind. African-descent and Latino individuals generally possess genomes of greater architectural complexity due to mosaic genomic ancestry, which can extensively and intricately impact phenotypic expression. As such, genetic analyses of admixed individuals require that genetic admixture be quantified to accurately model the impact of genetic variation on phenotypic expression. In this overview, we explore how fundamental genetic concepts such as linkage disequilibrium and differential allele frequency interact with genetic admixture to uniquely influence phenotypes in admixed individuals. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

A higher burden of multiple sclerosis genetic risk confers an earlier onset.

BACKGROUND: Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration. OBJECTIVES: Determine the influence of MS genetic predisposition on age of onset. METHODS: We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of HLA-DRB1*15:01 alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex. RESULTS: The mean age at onset was 32 years, 29% were male, and 46% were HLA-DRB1*15:01 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*15:01 alleles) were on average 5 years younger at onset (p = 0.002) than those with the lowest genetic risk burden (the lowest GRS quintile with no HLA-DRB1*15:01 alleles). There was a strong inverse relationship between the MS genetic risk burden and age at onset of MS (p < 5 × 10-8). CONCLUSION: We demonstrate a significant gradient between elevated MS genetic risk burden and an earlier onset of MS, suggesting that a higher MS genetic risk burden accelerates onset of the disease.

Depression in multiple sclerosis patients associated with risk variant near NEGR1.

BACKGROUND: A substantial number of patients diagnosed with multiple sclerosis (MS) suffer from depression in addition to physical symptoms and disability. Recent evidence suggests a stronger relationship may exist between MS and depression than previously thought, in which a diagnosis of depression may be prodromic to the development of MS. METHODS: A genome-wide association study (GWAS) was performed to identify genetic variants associated with the development of depression in a cohort of MS patients. The control group (n = 1180) was composed of MS patients with no diagnoses of depression as determined by ICD-9 and ICD-10 billing codes present in the electronic health record (EHR). Separate analyses were performed for three different case groups: 1) MS patients having a depression diagnosis at any time (n = 182), 2) MS patients having a depression diagnosis one year pre-MS diagnosis (n = 27), and 3) MS patients having a depression diagnosis one year post-MS diagnosis (n = 130). Logistic regression analyses were also performed to test for associations between the development of depression and an APOE tagging variant, as APOE was previously linked to depressive affect in MS. An additional logistic regression analysis tested for associations between depression in MS patients and SNPs associated with depression in the general population. Pathway enrichment analyses were also conducted to identify pathways that link the two diseases. RESULTS: GWAS identified no novel associations between variants and a diagnosis of depression relative to a diagnosis of MS. One variant, rs1432639, associated with depression in the general population, was significantly associated with the development of depression post-MS diagnosis. The APOE-related SNPs were not associated with depression in this study population. An IGF1 pathway approached statistical significance in patients diagnosed with depression prior to a diagnosis of MS. CONCLUSION: rs1432639 and the IGF1 pathway provide evidence for a genetic link between MS and depression that warrants further research.