Lydia Howell

Graduate Trainee, Brigham Young University

5 active projects

Infectious disease GWAS

I am interested in the connection between infectious disease and autoimmune disease, and investigating the hypothesis that a pathogen like herpes simplex virus or Mycobacterium tuberculosis which can cause chronic disease might potentially cause long-term immune disruption that would make…

Scientific Questions Being Studied

I am interested in the connection between infectious disease and autoimmune disease, and investigating the hypothesis that a pathogen like herpes simplex virus or Mycobacterium tuberculosis which can cause chronic disease might potentially cause long-term immune disruption that would make someone more susceptible to developing an autoimmune disease. Published research links infection with pathogens like herpes virus to lupus, arthritis, and multiple sclerosis. This hypothesis is important because autoimmune conditions like multiple sclerosis are not well understood and their etiology is unclear, with some combination of genetic predisposition and environmental factors leading to disease. Understanding the role of common infections in lowering the barriers to autoimmune disease is very important for better treatment and diagnosis of those diseases.

Project Purpose(s)

  • Disease Focused Research (Herpes and tuberculosis)

Scientific Approaches

I will be performing two GWAS studies on infection with tuberculosis and herpes simplex virus, using PLINK. I will be using a diverse sample and stratifying by genetic ancestry. I previously performed two PheWAS studies on tuberculosis and herpes simplex virus with the hypothesis that phecodes corresponding to autoimmune conditions will be among the significant results, and I will use the same diagnostic criteria for determining cases and controls, relying on lab tests for herpes simplex virus and a combination of lab tests and drug prescriptions for relevant drugs for tuberculosis.

Anticipated Findings

I hypothesize that the SNPs associated with infection with either of these two infections will be also linked to autoimmune conditions, strengthening the link between the autoimmune and infectious conditions. The large amount of genetic information on All of Us will contribute to the existing body of work on tuberculosis and herpes simplex virus, hopefully validating previous associations found between specific SNPs and infection with tuberculosis and herpes simplex virus. I anticipate that we will replicate previous results found in the limited number of GWAS studies on tuberculosis and herpes simplex virus and identify new genetic links to risk of tuberculosis and herpes simplex virus, which will hopefully overlap with known genetic links to autoimmune disease.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

  • Mary Davis - Early Career Tenure-track Researcher, Brigham Young University
  • Lydia Howell - Graduate Trainee, Brigham Young University

PheWAS TB & herpesvirus mfd

My research will aim to further clarify the links between infectious disease and later development of autoimmune or complex disease (based on the immunological disruption that many chronic infectious diseases can cause). This question is important because it can provide…

Scientific Questions Being Studied

My research will aim to further clarify the links between infectious disease and later development of autoimmune or complex disease (based on the immunological disruption that many chronic infectious diseases can cause). This question is important because it can provide further answers to how complex diseases like multiple sclerosis and Parkinson's disease develop, since their current etiology is not well understood and can only partially be explained by genetic predisposition.

Project Purpose(s)

  • Disease Focused Research (infectious diseases & autoimmune diseases)
  • Population Health
  • Ancestry

Scientific Approaches

This specific workspace will be used for a PheWAS (phenome-wide association study) procedure, where I will look for associations between either a herpesvirus or Mycobacterium tuberculosis infection and the phenotypes available through EHR data, focusing on phenotypes surrounding autoimmune disease. I will use EHR data including conditions, concepts, labs, and measurements, as well as WGS data.

Anticipated Findings

I anticipate finding links between infection and some complex diseases, because in general both herpesvirus and TB are linked to immune disruption. This will add to the current models for development of autoimmune or complex diseases, clarifying the balance between genetic and environmental factors that lead to autoimmune or complex diseases. This will also add to our understanding of the long-term implications of infection.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

  • Mary Davis - Early Career Tenure-track Researcher, Brigham Young University
  • Lydia Howell - Graduate Trainee, Brigham Young University

PheWAS TB & herpesvirus mfd 051024

My research will aim to further clarify the links between infectious disease and later development of autoimmune or complex disease (based on the immunological disruption that many chronic infectious diseases can cause). This question is important because it can provide…

Scientific Questions Being Studied

My research will aim to further clarify the links between infectious disease and later development of autoimmune or complex disease (based on the immunological disruption that many chronic infectious diseases can cause). This question is important because it can provide further answers to how complex diseases like multiple sclerosis and Parkinson's disease develop, since their current etiology is not well understood and can only partially be explained by genetic predisposition.

Project Purpose(s)

  • Disease Focused Research (infectious diseases & autoimmune diseases)
  • Population Health
  • Ancestry

Scientific Approaches

This specific workspace will be used for a PheWAS (phenome-wide association study) procedure, where I will look for associations between either a herpesvirus or Mycobacterium tuberculosis infection and the phenotypes available through EHR data, focusing on phenotypes surrounding autoimmune disease. I will use EHR data including conditions, concepts, labs, and measurements, as well as WGS data.

Anticipated Findings

I anticipate finding links between infection and some complex diseases, because in general both herpesvirus and TB are linked to immune disruption. This will add to the current models for development of autoimmune or complex diseases, clarifying the balance between genetic and environmental factors that lead to autoimmune or complex diseases. This will also add to our understanding of the long-term implications of infection.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

  • Mary Davis - Early Career Tenure-track Researcher, Brigham Young University
  • Lydia Howell - Graduate Trainee, Brigham Young University

Metabolism v7 mfd

Metabolic diseases are a global epidemic. They occur when cells allocate too many of their primary resources towards one pathway, such as lipid production, at the expense of other crucial pathways, such as energy production. Understanding how cells control the…

Scientific Questions Being Studied

Metabolic diseases are a global epidemic. They occur when cells allocate too many of their primary resources towards one pathway, such as lipid production, at the expense of other crucial pathways, such as energy production. Understanding how cells control the pivotal point of allocating glucose towards lipid or energy production is key to developing effective treatments for these and other common metabolic diseases. PAS kinase (PASK) is a nutrient sensing protein kinase that regulates this critical metabolic node of lipid versus respiratory metabolism. PASK controls many of the hallmark pathways associated with heart disease, diabetes, cancer, and even neurodegenerative disease yet little is known about PASK alleles associated with human disease. Herein we propose to conduct the first large-scale analysis to identify PASK alleles associated with human disease.

Project Purpose(s)

  • Ancestry

Scientific Approaches

Analyze common and rare variants in USF1, ATXN2, and PASK compared to triglycerides, weight, cardiovascular measures, exercise levels and COVID-19 results.

Perform a phenome-wide association study (PheWAS) with common and rare variants in USF1, ATXN2, and PASK. Common variants in each of these three genes will be regressed against phenotypes from electronic health record data.

Anticipated Findings

We target PASK as well as two of its substrates for our study. Due to their regulation of the critical node of glucose partitioning to lipid versus respiratory metabolism, we propose to uncover the influence of PASK, USF1, and ATXN2 variants on a variety of human phenotypes and classes of disease, from hyperlipidemia and diabetes to neurodegenerative disorders using the All of Us dataset.
In addition to the wide variety of phenotypic data that will aid in understanding the influence of variation in cellular respiration and triglyceride levels, the ancestral diversity represented by the individuals in the dataset will allow us to identify patterns and variants that differ or are similar across ancestry, defining effects common to humankind while opening further studies on multigene, secondary variants.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

  • Miranda Sharp - Graduate Trainee, Brigham Young University
  • Mary Davis - Early Career Tenure-track Researcher, Brigham Young University
  • Lydia Howell - Graduate Trainee, Brigham Young University
  • Kylee Bates - Undergraduate Student, Brigham Young University

Collaborators:

  • Breckin Forstrom - Undergraduate Student, Brigham Young University
  • Christian Betteridge - Undergraduate Student, Brigham Young University
  • Alyks Odell - Undergraduate Student, Brigham Young University

Metabolism v7

Metabolic diseases are a global epidemic. They occur when cells allocate too many of their primary resources towards one pathway, such as lipid production, at the expense of other crucial pathways, such as energy production. Understanding how cells control the…

Scientific Questions Being Studied

Metabolic diseases are a global epidemic. They occur when cells allocate too many of their primary resources towards one pathway, such as lipid production, at the expense of other crucial pathways, such as energy production. Understanding how cells control the pivotal point of allocating glucose towards lipid or energy production is key to developing effective treatments for these and other common metabolic diseases. PAS kinase (PASK) is a nutrient sensing protein kinase that regulates this critical metabolic node of lipid versus respiratory metabolism. PASK controls many of the hallmark pathways associated with heart disease, diabetes, cancer, and even neurodegenerative disease yet little is known about PASK alleles associated with human disease. Herein we propose to conduct the first large-scale analysis to identify PASK alleles associated with human disease.

Project Purpose(s)

  • Ancestry

Scientific Approaches

Analyze common and rare variants in USF1, ATXN2, and PASK compared to triglycerides, weight, cardiovascular measures, exercise levels and COVID-19 results.

Perform a phenome-wide association study (PheWAS) with common and rare variants in USF1, ATXN2, and PASK. Common variants in each of these three genes will be regressed against phenotypes from electronic health record data.

Anticipated Findings

We target PASK as well as two of its substrates for our study. Due to their regulation of the critical node of glucose partitioning to lipid versus respiratory metabolism, we propose to uncover the influence of PASK, USF1, and ATXN2 variants on a variety of human phenotypes and classes of disease, from hyperlipidemia and diabetes to neurodegenerative disorders using the All of Us dataset.
In addition to the wide variety of phenotypic data that will aid in understanding the influence of variation in cellular respiration and triglyceride levels, the ancestral diversity represented by the individuals in the dataset will allow us to identify patterns and variants that differ or are similar across ancestry, defining effects common to humankind while opening further studies on multigene, secondary variants.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

  • Mary Davis - Early Career Tenure-track Researcher, Brigham Young University
  • Lydia Howell - Graduate Trainee, Brigham Young University
  • Kylee Bates - Undergraduate Student, Brigham Young University
  • Christian Betteridge - Undergraduate Student, Brigham Young University

Collaborators:

  • Spencer Boris - Undergraduate Student, Brigham Young University
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