Health inequities in SARS-CoV-2 infection, seroprevalence, and COVID-19 vaccination: Results from the East Bay COVID-19 study.

Comprehensive data on transmission mitigation behaviors and both SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify COVID-19 risk factors and the impact of public health measures. We conducted a longitudinal, population-based study in the East Bay Area of Northern California. From July 2020-March 2021, approximately 5,500 adults were recruited and followed over three data collection rounds to investigate the association between geographic and demographic characteristics and transmission mitigation behavior with SARS-CoV-2 prevalence.

Cross-Trait Mendelian Randomization Study to Investigate Whether Migraine Is a Risk Factor for Multiple Sclerosis.

Background And Objectives: Migraine is common among people with multiple sclerosis (MS), but the reasons for this are unknown. We tested 3 hypothesized mechanisms for this observed comorbidity, including migraine is a risk factor of MS, genetic variants are shared between the conditions, and migraine is because of MS.

Methods: Data were from 2 sources: publicly available summary statistics from genome-wide association studies of MS (N = 115,748) and migraine (N = 375,752 and N = 361,141) and a case-control study of MS recruited from the Kaiser Permanente Northern California Health Plan (N = 1,991).

Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies.

Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed.

Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans.

Polygenic inheritance plays a pivotal role in driving multiple sclerosis susceptibility, an inflammatory demyelinating disease of the CNS. We developed polygenic risk scores (PRS) of multiple sclerosis and assessed associations with both disease status and severity in cohorts of European descent. The largest genome-wide association dataset for multiple sclerosis to date (n = 41 505) was leveraged to generate PRS scores, serving as an informative susceptibility marker, tested in two independent datasets, UK Biobank [area under the curve (AUC) = 0.

Case-control study of adverse childhood experiences and multiple sclerosis risk and clinical outcomes.

Background: Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study's objective was to test for the association between ACEs and MS risk and several clinical outcomes.

Methods: We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California.

Gene-environment interactions increase the risk of pediatric-onset multiple sclerosis associated with ozone pollution.

Background: We previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure.

Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome.

Identifying the effects of genetic variation on the epigenome in disease-relevant cell types can help advance our understanding of the first molecular contributions of genetic susceptibility to disease onset. Here, we establish a genome-wide map of DNA methylation quantitative trait loci in CD4 T-cells isolated from multiple sclerosis patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both multiple sclerosis susceptibility and local DNA methylation.

Gut microbiome is associated with multiple sclerosis activity in children.

Objective: To identify features of the gut microbiome associated with multiple sclerosis activity over time.

Methods: We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses.

Seafood, fatty acid biosynthesis genes, and multiple sclerosis susceptibility.

Background: The role of omega-3 fatty acid in multiple sclerosis (MS) susceptibility is unclear.

Objective: To determine whether fish/seafood intake or genetic factors that regulate omega-3 fatty acids levels are associated with MS risk.

Methods: We examined the association of fish and shrimp consumption and 13 tag single nucleotide polymorphisms (SNPs) in , and with risk of MS in 1153 individuals from the MS Sunshine Study, a case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California.

Pregnancy does not modify the risk of MS in genetically susceptible women.

Objective: To use the case-only gene-environment (G [Formula: see text] E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females.

Methods: We studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) [Formula: see text] live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms.

A validation study for remote testing of cognitive function in multiple sclerosis.

Objectives: Determine the validity and reliability of a remote, technician-guided cognitive assessment for multiple sclerosis (MS), incorporating the Symbol Digit Modalities Test (SDMT) and the California Verbal Learning Test, Second Edition (CVLT-II).

Methods: In 100 patients, we compared conventional in-person testing to remote, web-assisted assessments, and in 36 patients, we assessed test-retest reliability using two equivalent, alternative forms.

Results: In-person and remote-administered SDMT ( = 0.

Global expression and CpG methylation analysis of primary endothelial cells before and after TNFa stimulation reveals gene modules enriched in inflammatory and infectious diseases and associated DMRs.

Endothelial cells are a primary site of leukocyte recruitment during inflammation. An increase in tumor necrosis factor-alpha (TNFa) levels as a result of infection or some autoimmune diseases can trigger this process. Several autoimmune diseases are now treated with TNFa inhibitors.

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

Objective: Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS.

Vitamin D genes influence MS relapses in children.

Objective: The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children.

Methods: DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS).

Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry.

Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors.

Mother-child histocompatibility and risk of rheumatoid arthritis and systemic lupus erythematosus among mothers.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags).

Heterogeneity in association of remote herpesvirus infections and pediatric MS.

Objective: While prior Epstein-Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections.

Methods: Cases with pediatric-onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers.

Incorporating machine learning approaches to assess putative environmental risk factors for multiple sclerosis.

Background: Multiple sclerosis (MS) incidence has increased recently, particularly in women, suggesting a possible role of one or more environmental exposures in MS risk. The study objective was to determine if animal, dietary, recreational, or occupational exposures are associated with MS risk.

Methods: Least absolute shrinkage and selection operator (LASSO) regression was used to identify a subset of exposures with potential relevance to disease in a large population-based (Kaiser Permanente Northern California [KPNC]) case-control study.

BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia.

Genome-wide association studies of childhood acute lymphoblastic leukemia (ALL) have identified regions of association at PIP4K2A and upstream of BMI1 at chromosome 10p12.31-12.2.

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

Objective: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients.

Methods: Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein).

Genetic risk factors for pediatric-onset multiple sclerosis.

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.

Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.

Methods: Cases with onset <18 years ( = 569) and controls ( = 16,251) were included from the United States and Sweden.