Farren Briggs
UC Berkeley, Epidemiology, Graduate Student
Background: The incidence of acute lymphoblastic leukemia (ALL) is nearly 20% higher among Hispanics than non-Hispanic Whites. Previous studies have shown evidence for association between risk of ALL and variation within IKZF1, ARID5B,... more
Background: The incidence of acute lymphoblastic leukemia (ALL) is nearly 20% higher among Hispanics than non-Hispanic Whites. Previous studies have shown evidence for association between risk of ALL and variation within IKZF1, ARID5B, CEBPE, CDKN2A, GATA3, and BM1-PIP4K2A genes. However, variants identified only account for <10% of the genetic risk of ALL. Methods: We applied pathway-based analyses to genome-wide association study (GWAS) data from the California Childhood Leukemia Study to determine whether different biologic pathways were overrepresented in childhood ALL and major ALL subtypes. Furthermore, we applied causal inference and data reduction methods to prioritize candidate genes within each identified overrepresented pathway, while accounting for correlation among SNPs. Results: Pathway analysis results indicate that different ALL subtypes may involve distinct biologic mechanisms. Focal adhesion is a shared mechanism across the different disease subtypes. For ALL, t...
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Introduction: Tobacco smoke exposure is an established risk factor for multiple sclerosis (MS), yet how it confers risk is not known. Evidence from observational studies suggests nicotine may be a protective component. Animal studies... more
Introduction: Tobacco smoke exposure is an established risk factor for multiple sclerosis (MS), yet how it confers risk is not known. Evidence from observational studies suggests nicotine may be a protective component. Animal studies further support this hypothesis, demonstrating nicotine’s protective effect in MS is mediated by the presence and absence of α7 and α9 nicotinic acetylcholine receptors (nAChRs), respectively. Objective: To determine if variation in the genes encoding α7 and α9 nAChRs (cholinergic receptor nicotinic alpha 7 ( CHRNA7) and alpha 9 ( CHRNA9)) will modify MS risk conferred by tobacco smoking. Methods: A multi-stage gene-environment (G×E) framework was utilized, including a case–control analysis (286 cases, 176 controls) with haplotype- and gene-based analyses, followed by an extension case-only (1053 cases) analysis for overlapping variants. Results: The results suggest that CHRNA7 and CHRNA9 modifies MS risk conferred by tobacco smoke, where risk among smo...
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Background: Persons with multiple sclerosis (PwMS) are disproportionately burdened by depression compared to the general population. While several factors associated with depression and depression severity in PwMS have been identified, a... more
Background: Persons with multiple sclerosis (PwMS) are disproportionately burdened by depression compared to the general population. While several factors associated with depression and depression severity in PwMS have been identified, a prediction model for depression risk has not been developed. In addition, it is unknown if depression-related genetic variants, including Apolipoprotein E ( APOE), would be informative for predicting depression in PwMS. Objective: To develop a depression prediction model for PwMS who did not have a history of depression prior MS onset. Methods: The study population included 917 non-Hispanic white PwMS. An optimized multivariable Cox proportional hazards model for time to depression was generated using non-genetic variables, to which APOE and a depression-related genetic risk score were included. Results: Having a mother who had a history of depression, having obstructive pulmonary disease, obesity and other physical disorders at MS onset, and affect...
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Background/objective: In 2019, the 2010 U.S. multiple sclerosis (MS) prevalence was robustly estimated (265.1–309.2/100,000) based on large administrative health-claims datasets. Using 56.6 million electronic health records (EHRs), we... more
Background/objective: In 2019, the 2010 U.S. multiple sclerosis (MS) prevalence was robustly estimated (265.1–309.2/100,000) based on large administrative health-claims datasets. Using 56.6 million electronic health records (EHRs), we sought to generate complementary age, sex, and race standardized estimates. Methods/results: Using de-identified EHRs and 2018 U.S. Census data, we estimated an age- and sex-standardized MS prevalence of 219.5/100,000 which increased to 274.5/100,000 when accounting for White and Black race alone. Women aged 50 to 69 years had the highest prevalence (>600/100,000). Among White and Black Americans, the age- and sex-standardized prevalence was 283.7 and 226.1 per 100,000, respectively. Conclusion: Using 56.6 million EHRs and standardizing for age, sex, and race (White and Black Americans only), we estimated at least 810,504 Americans were living with MS in 2018.
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Background Opportunistic infections (OIs) are more common in patients with inflammatory bowel disease (IBD); however, there have been limited large-scale studies of OIs in IBD. We investigated the epidemiological characteristics of OI in... more
Background Opportunistic infections (OIs) are more common in patients with inflammatory bowel disease (IBD); however, there have been limited large-scale studies of OIs in IBD. We investigated the epidemiological characteristics of OI in Crohn’s disease (CD) and ulcerative colitis (UC) using a large population-based database. Methods Data were collected from a commercial database (Explorys Inc., Cleveland, OH, USA) that provided electronic health records from 26 major integrated US health care systems from 1999 to March 2018. In this data set, we identified all CD and UC patients, based on Systemized Nomenclature of Medicine–Clinical Terms. Within these cohorts, we identified a variety of OIs and compared the prevalence rate of OI in individuals with IBD with that of controls (patients in the database between March 2013 and March 2018 without the diagnosis of IBD). Results Explorys included 153,290 patients with CD and 128,540 patients with UC between March 2013 and March 2018. The ...
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The phenotypic presentation of multiple sclerosis (MS) may predict long-term outcomes and little is known about factors contributing to heterogeneity at MS onset. Given temporality, it is likely MS risk factors also influence presentation... more
The phenotypic presentation of multiple sclerosis (MS) may predict long-term outcomes and little is known about factors contributing to heterogeneity at MS onset. Given temporality, it is likely MS risk factors also influence presentation of the disease near onset. Using a retrospective cross-sectional study of MS cases, we investigated: age of onset (AOO), number of impaired functional domains (NIFDs), time to second relapse (TT2R), and early relapse activity (ERA). Machine learning variable selection was applied to epidemiologic data for each outcome, followed by multivariable regression models. The models were further adjusted for HLA-DRB1*15:01 carrier status and a MS genetic risk score (GRS). The TT2R and ERA analyses were restricted to relapsing remitting MS cases. HLA-DRB1*15:01, GRS, and smoking were associated with earlier AOO. Cases who were male, obese, had lower education, or had primary progressive MS were older at onset. For NIFDs, those with relapsing remitting MS and of lower SES had increased NIFDs. Among relapsing remitting cases, those who were older at onset, obese, and had polyfocal presentation had shorter TT2R, while ERA was greater among those younger at onset and who were obese. Individual characteristics including age, genetic profiles, obesity, and smoking status contribute to heterogeneity in disease presentation and modulate early disease course evolution.
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The impact of underlying immune-mediated inflammatory diseases (IMID) in patients undergoing hematopoietic stem cell transplant (HSCT) is unclear. Hematopoietic cell transplantation co-morbidity index (HCT-CI) is gaining acceptance as a... more
The impact of underlying immune-mediated inflammatory diseases (IMID) in patients undergoing hematopoietic stem cell transplant (HSCT) is unclear. Hematopoietic cell transplantation co-morbidity index (HCT-CI) is gaining acceptance as a reliable clinical method to score pre-transplant co-morbidities. Higher HCT-CI from a co-morbid IMID implies higher NRM. However, HCT-CI integrates many IMIDs with different pathogenesis and treatment together which may lead to spurious results. We performed a cross-sectional study using Nationwide Inpatient Sample dataset from 1998 to 2011 to compare the outcomes of HSCT in patients with different co-morbid IMIDs with patients without any co-morbid IMIDs. In both our multivariate and stringent matched-pair analysis, ulcerative colitis (UC) was associated with increased mortality while rheumatoid arthritis and psoriasis were associated with lower mortality as compared to no IMID group. Furthermore, in allogeneic HSCT subgroup, UC was associated with ...
Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive... more
Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study pa...
Tobacco smoke plays a pathogenic role in multiple sclerosis (MS) and may accelerate disease progression, yet, some people with MS continue to smoke after disease onset. The average smoker reports diminished health-related quality of life... more
Tobacco smoke plays a pathogenic role in multiple sclerosis (MS) and may accelerate disease progression, yet, some people with MS continue to smoke after disease onset. The average smoker reports diminished health-related quality of life (HRQOL) across many populations. To describe the relationships between smoking status and HRQOL, disease activity, and global disability in a US population with MS. We compared smokers to non-smokers in 950 responders to the Spring 2014 update survey completed by North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants. HRQOL was assessed using Short Form-12 version 2 (SF-12v2), disease activity was investigated using eight Performance Scales (PS) and three Functionality Scales (FS). Global disability was evaluated using Patient Determined Disease Steps (PDDS) and an item response theory (IRT) summed score based on the PS and FS. Smokers had lower HRQOL ( p < 0.0001), reported more disease activity ( p < 0.05) an...
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Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7... more
Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk. Importantly, this DDX39B variant showed strong genetic and functional epistasis with allelic variants in IL7R exon 6. This study establishes the occurrence of biological epistasis in humans and provides mechanistic insight into the regulation of IL7R exon 6 splicing and its impact on MS risk.
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To compare the times to evaluation and thrombolytic treatment of patients treated with a telemedicine-enabled mobile stroke treatment unit (MSTU) vs those among patients brought to the emergency department (ED) via a traditional... more
To compare the times to evaluation and thrombolytic treatment of patients treated with a telemedicine-enabled mobile stroke treatment unit (MSTU) vs those among patients brought to the emergency department (ED) via a traditional ambulance. We implemented a MSTU with telemedicine at our institution starting July 18, 2014. A vascular neurologist evaluated each patient via telemedicine and a neuroradiologist and vascular neurologist remotely assessed images obtained by the MSTU CT. Data were entered in a prospective registry. The evaluation and treatment of the first 100 MSTU patients (July 18, 2014-November 1, 2014) was compared to a control group of 53 patients brought to the ED via a traditional ambulance in 2014. Times were expressed as medians with their interquartile ranges. Patient and stroke severity characteristics were similar between 100 MSTU and 53 ED control patients (initial NIH Stroke Scale score 6 vs 7, p = 0.679). There was a significant reduction of median alarm-to-CT...
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Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of... more
Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG sites, BACH2, INS-IGF2, and CLEC16A (DNAm difference range: 2.2%-5.0%). In the epigenome CpG set, the greatest methylation differences were observed in MAGI2, FANCC, and PCDHB16, (DNAm difference range: 6.9%-16.1%). These findings were not observed in the HLA-identical NTS pairs. Targeted pyrosequencing of five candidate CpG loci identified using the 450k array in the original discordant MZ twins produced similar results using control DNA samples, indicating strong agreement between the two DNA methylation profiling platforms. However, findings for the top five candidate CpG loci were not replicated in six additional T1D-discordant MZ twin pairs. Our results indicate global DNA hypomethylation within gene promoter regions may contribute to T1D; however, findings do not support the involvement of large DNAm differences at single CpG sites alone in T1D.
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Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical... more
Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical medicine has tended to rely on comparisons of fit metrics like C-statistics. However, for many data adaptive modelling procedures such approaches are not suitable. In these cases, statisticians have used cross-validation, which can make inference challenging. In this paper we propose a general approach that focuses on the “conditional” risk difference (conditional on the model fits being fixed) for the improvement in prediction risk. Specifically, we derive a Wald-type test statistic and associated confidence intervals for cross-validated test sets utilizing the independent validation within cross-validation in conjunction with a test for multiple comparisons. We show that this test maintains proper Type I Error under the null fit, and can be used as a g...
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Mobile stroke treatment units (MSTUs) with on-site treatment teams that include a vascular neurologist can provide thrombolysis in the prehospital setting faster than treatment in the hospital. These units can be made more resource... more
Mobile stroke treatment units (MSTUs) with on-site treatment teams that include a vascular neurologist can provide thrombolysis in the prehospital setting faster than treatment in the hospital. These units can be made more resource efficient if the need for an on-site neurologist can be eliminated by relying solely on telemedicine for physician presence. To test whether telemedicine is reliable and remote physician presence is adequate for acute stroke treatment using an MSTU. Prospective observational study conducted between July 18 and November 1, 2014. The dates of the study analysis were November 1, 2014, to March 30, 2015. The setting was a community-based study assessing telemedicine success of the MSTU in Cleveland, Ohio. Participants were the first 100 residents of Cleveland who had an acute onset of stroke-like symptoms between 8 am and 8 pm and were evaluated by the MSTU after the implementation of the MSTU program at the Cleveland Clinic. A vascular neurologist evaluated ...
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Multiple sclerosis (MS) is a debilitating autoimmune disease with a prominent inflammatory component. There have been strides identifying genetic and environmental MS risk factors, though much of the disease risk remains unknown. Recent... more
Multiple sclerosis (MS) is a debilitating autoimmune disease with a prominent inflammatory component. There have been strides identifying genetic and environmental MS risk factors, though much of the disease risk remains unknown. Recent large observational studies suggest adverse socioeconomic position increases the risk for MS, however the mediating biological processes are not understood. We hypothesize a prominent role for stress response, both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which become maladaptive under frequent or chronic stimulation resulting in a proinflammatory phenotype. Thus, adverse SEP and chronic stress may predispose individuals for MS.
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Favorable outcomes in intraarterial therapy (IAT) for acute ischemic stroke (AIS) are related to early vessel recanalization. The mobile stroke treatment unit (MSTU) is an on-site, prehospital, treatment team, laboratory, and CT scanner... more
Favorable outcomes in intraarterial therapy (IAT) for acute ischemic stroke (AIS) are related to early vessel recanalization. The mobile stroke treatment unit (MSTU) is an on-site, prehospital, treatment team, laboratory, and CT scanner that reduces time to treatment for intravenous thrombolysis and may also shorten time to IAT. Using our MSTU database, we identified patients that underwent IAT for AIS. We compared the key time metrics to historical controls, which included patients that underwent IAT at our institution six months prior to implementation of the MSTU. We further divided the controls into two groups: (1) transferred to our institution for IAT and (2) directly presented to our emergency room and underwent IAT. After 164 days of service, the MSTU transported 155 patients of which 5 underwent IAT. We identified 5 historical controls that were transferred to our center for IAT. Substantial reduction in times including median door to initial CT (12 minute vs. 32 minute), C...
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Determine whether MS-specific DNA methylation profiles can be identified in whole blood or purified immune cells from untreated MS patients. Whole blood, CD4+ and CD8+ T cell DNA from 16 female, treatment naïve MS patients and 14 matched... more
Determine whether MS-specific DNA methylation profiles can be identified in whole blood or purified immune cells from untreated MS patients. Whole blood, CD4+ and CD8+ T cell DNA from 16 female, treatment naïve MS patients and 14 matched controls was profiled using the HumanMethylation450K BeadChip. Genotype data were used to assess genetic homogeneity of our sample and to exclude potential SNP-induced DNA methylation measurement errors. As expected, significant differences between CD4+ T cells, CD8+ T cells and whole blood DNA methylation profiles were observed, regardless of disease status. Strong evidence for hypermethylation of CD8+ T cell, but not CD4+ T cell or whole blood DNA in MS patients compared to controls was observed. Genome-wide significant individual CpG-site DNA methylation differences were not identified. Furthermore, significant differences in gene DNA methylation of 148 established MS-associated risk genes were not observed. While genome-wide significant DNA meth...
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There is a strong and complex genetic component to multiple sclerosis (MS). In addition to variation in the major histocompatibility complex (MHC) region on chromosome 6p21.3, 110 non-MHC susceptibility variants have been identified in... more
There is a strong and complex genetic component to multiple sclerosis (MS). In addition to variation in the major histocompatibility complex (MHC) region on chromosome 6p21.3, 110 non-MHC susceptibility variants have been identified in Northern Europeans, thus far. The majority of the MS-associated genes are immune related; however, similar to most other complex genetic diseases, the causal variants and biological processes underlying pathogenesis remain largely unknown. We created a comprehensive catalog of putative functional variants that reside within linkage disequilibrium regions of the MS-associated genic variants to guide future studies. Bioinformatics analyses were also conducted using publicly available resources to identify plausible pathological processes relevant to MS and functional hypotheses for established MS-associated variants.
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Genome-wide association studies focusing on European-ancestry populations have identified ALL risk loci on IKZF1, ARID5B, and CEBPE. To capture the impacts of these genes on ALL risk in the California Hispanic population, we... more
Genome-wide association studies focusing on European-ancestry populations have identified ALL risk loci on IKZF1, ARID5B, and CEBPE. To capture the impacts of these genes on ALL risk in the California Hispanic population, we comprehensively assessed the variation within the genes and further assessed the joint effects between the genetic variation and surrogates for early-life infections (the presence of older siblings, daycare attendance, and ear infections). Genotypic data for 323 Hispanic ALL cases and 454 controls from the California Childhood Leukemia Study were generated using Illumina OmniExpress v1 platform. Logistic regression assuming a log-additive model estimated odds ratios (OR) associated with each SNP, adjusted for age, sex, and the first five principal components. In addition, we examined potential interactions between six ALL risk alleles and surrogates for early-life infections using logistic regression models that included an interaction term. Significant associations between genotypes at IKZF1, ARID5B, and CEBPE and ALL risk were identified: rs7780012, OR 0.50, 95 % confidence interval (CI) 0.35-0.71 (p = 0.004); rs7089424, OR 2.12, 95 % CI 1.70-2.65 (p = 1.16 × 10(-9)); rs4982731, OR 1.69, 95 % CI 1.37-2.08 (p = 2.35 × 10(-6)), respectively. Evidence for multiplicative interactions between genetic variants and surrogates for early-life infections with ALL risk was not observed. Consistent with findings in non-Hispanic White population, our study showed that variants within IKZF1, ARID5B, and CEBPE were associated with increased ALL risk, and the effects for ARID5B and CEBPE were most prominent in the high-hyperdiploid ALL subtype in the California Hispanic population. Results implicate the ARID5B, CEBPE, and IKZF1 genes in the pathogenesis of childhood ALL.
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To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California... more
To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling dem...
Research Interests: Multiple sclerosis, Obesity, Disease susceptibility, California, Humans, and 15 moreChild, Female, Male, Body Size, Body Mass Index, Risk factors, Middle Aged, Adult, Odds ratio, Age Factors, Pediatric Obesity, Risk Factors, Logistic Models, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases... more
Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay. Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive. Sensi...
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The Random Forests (RF) algorithm has become a commonly used machine learning algorithm for genetic association studies. It is well suited for genetic applications since it is both computationally efficient and models genetic causal... more
The Random Forests (RF) algorithm has become a commonly used machine learning algorithm for genetic association studies. It is well suited for genetic applications since it is both computationally efficient and models genetic causal mechanisms well. With its growing ubiquity, there has been inconsistent and less than optimal use of RF in the literature. The purpose of this review is to breakdown the theoretical and statistical basis of RF so that practitioners are able to apply it in their work. An emphasis is placed on showing how the various components contribute to bias and variance, as well as discussing variable importance measures. Applications specific to genetic studies are highlighted. To provide context, RF is compared to other commonly used machine learning algorithms.
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Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease.... more
Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease. The objective was to determine whether SEP over the life course confers increased susceptibility to MS. 1643 white, non-Hispanic MS case and control members recruited from the Kaiser Permanente Medical Care Plan, Northern California Region, for which comprehensive genetic, clinical and environmental exposure data have been collected were studied. Logistic regression models investigated measures of childhood and adulthood SEP, and accounted for effects due to established MS risk factors, including HLA-DRB1*15:01 allele carrier status, smoking history, history of infectious mononucleosis, family history of MS and body size. Multiple measures of childhood and adulthood SEP were significantly associated with risk of MS, including parents renting versus owning a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college education versus at least a college education based on parental household: OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50, 95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95% CI 1.27 to 2.39, p=5.7×10(-4). Results derived from a population-representative case-control study provide support for the role of adverse SEP in MS susceptibility and add to the growing evidence linking lower SEP to poorer health outcomes. Both genetic and environmental contributions to chronic conditions are important and must be characterised to fully understand MS aetiology.