Megan Lancaster

Research Fellow, Vanderbilt University Medical Center

5 active projects

Duplicate of How to Work with All of Us Genomic Data (Hail - Plink)(v6)

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Scientific Questions Being Studied

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Project Purpose(s)

  • Other Purpose (Demonstrate to the All of Us Researcher Workbench users how to get started with the All of Us genomic data and tools. It includes an overview of all the All of Us genomic data and shows some simple examples on how to use these data.)

Scientific Approaches

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Anticipated Findings

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

SMARD1

We are studying the genetics of spinal muscular atrophy with respiratory distress type 1. This is a rare, inherited, severely debilitating disease with onset in infancy. While this is most commonly caused when an individual inherits a copy of the…

Scientific Questions Being Studied

We are studying the genetics of spinal muscular atrophy with respiratory distress type 1. This is a rare, inherited, severely debilitating disease with onset in infancy. While this is most commonly caused when an individual inherits a copy of the causative variant (mutation) from each parent (autosomal recessive inheritance), we hypothesize that inheritance can be more complex than this.

Project Purpose(s)

  • Disease Focused Research (Spinal muscular atrophy with respiratory distress)

Scientific Approaches

We will use whole genome sequencing data from the All of Us to search for rare variants (mutations) in genes known and hypothesized to be causative in SMARD1. We will then compare this to the phenotypic data available in All of Us, looking specifically at neuromuscular symptoms and diagnoses.

Anticipated Findings

Understanding the genetics of SMARD1 will help us to better understand disease risk in individuals and their offspring, and to guide precision treatments.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

Duplicate of S1103Y sodium channel variant phenotypes

The S1103Y variant in the cardiac sodium channel gene has been associated with type 3 congenital long QT syndrome and drug-induced long QT syndrome in several reports. However, this variant is too common in African American populations, with an allele…

Scientific Questions Being Studied

The S1103Y variant in the cardiac sodium channel gene has been associated with type 3 congenital long QT syndrome and drug-induced long QT syndrome in several reports. However, this variant is too common in African American populations, with an allele frequency of 8.1%, to be highly pathogenic at baseline. Recent research in our lab in induced pluripotent stem cell derived cardiomyocytes has demonstrated that while this variant causes increased late sodium current, which should prolong the QT interval, the QT interval in these cells is not prolonged due to compensatory changes in other ion currents.

Project Purpose(s)

  • Ancestry

Scientific Approaches

I plan to use the genomic array datasets in patients with African ancestry to find participants who are homozygous for the S1103Y variant, heterozygous for the variant, and those who do not carry the variant. I will then examine the association between S1103Y carrier status and ECG metrics such as the QT interval, as well as arrhythmia phenotypes in patients without diagnosed cardiovascular disease. I will then examine the contribution of this variant to a polygenic risk estimation of the QT interval, with attention to interaction with other ion channel protein-encoding and regulatory genes.

Anticipated Findings

I anticipate that the S1103Y variant will associate with QT interval prolongation and cases of drug-induced long QT, but with a smaller effect size than classic monogenic variant causes of long QT syndrome. I expect that the presence of the S1103Y variant will add to a polygenic risk assessment for long QT. I expect that the S1103Y variant will co-segregate with other cardiac ion channel-related genes.

Demographic Categories of Interest

  • Race / Ethnicity

Data Set Used

Controlled Tier

Research Team

Owner:

Duplicate of How to Work with All of Us Genomic Data (Hail - Plink)

Validation of alpha 0 genomic data. Validation of alpha 0 genomic data. Validation of alpha 0 genomic data.

Scientific Questions Being Studied

Validation of alpha 0 genomic data. Validation of alpha 0 genomic data. Validation of alpha 0 genomic data.

Project Purpose(s)

  • Educational

Scientific Approaches

Validation of alpha 0 genomic data. Validation of alpha 0 genomic data. Validation of alpha 0 genomic data.

Anticipated Findings

Validation of alpha 0 genomic data. Validation of alpha 0 genomic data. Validation of alpha 0 genomic data.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

S1103Y sodium channel variant phenotypes

The S1103Y variant in the cardiac sodium channel gene has been associated with type 3 congenital long QT syndrome and drug-induced long QT syndrome in several reports. However, this variant is too common in African American populations, with an allele…

Scientific Questions Being Studied

The S1103Y variant in the cardiac sodium channel gene has been associated with type 3 congenital long QT syndrome and drug-induced long QT syndrome in several reports. However, this variant is too common in African American populations, with an allele frequency of 8.1%, to be highly pathogenic at baseline. Recent research in our lab in induced pluripotent stem cell derived cardiomyocytes has demonstrated that while this variant causes increased late sodium current, which should prolong the QT interval, the QT interval in these cells is not prolonged due to compensatory changes in other ion currents.

Project Purpose(s)

  • Ancestry

Scientific Approaches

I plan to use the genomic array datasets in patients with African ancestry to find participants who are homozygous for the S1103Y variant, heterozygous for the variant, and those who do not carry the variant. I will then examine the association between S1103Y carrier status and ECG metrics such as the QT interval, as well as arrhythmia phenotypes in patients without diagnosed cardiovascular disease. I will then examine the contribution of this variant to a polygenic risk estimation of the QT interval, with attention to interaction with other ion channel protein-encoding and regulatory genes.

Anticipated Findings

I anticipate that the S1103Y variant will associate with QT interval prolongation and cases of drug-induced long QT, but with a smaller effect size than classic monogenic variant causes of long QT syndrome. I expect that the presence of the S1103Y variant will add to a polygenic risk assessment for long QT. I expect that the S1103Y variant will co-segregate with other cardiac ion channel-related genes.

Demographic Categories of Interest

  • Race / Ethnicity

Data Set Used

Controlled Tier

Research Team

Owner:

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