Michelle Mcnulty
A5076912677- Renal Diseases and Glomerulopathies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Chronic Kidney Disease and Diabetes
- Genetic Associations and Epidemiology
- Chronic Lymphocytic Leukemia Research
- Celiac Disease Research and Management
- Systemic Lupus Erythematosus Research
- Renal and related cancers
- Birth, Development, and Health
- Gene expression and cancer classification
- Systemic Sclerosis and Related Diseases
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Cerebrovascular and genetic disorders
- Renin-Angiotensin System Studies
- RNA regulation and disease
- Statistical Methods and Inference
- Hormonal Regulation and Hypertension
- Reproductive System and Pregnancy
- Biomedical Research and Pathophysiology
- Electrolyte and hormonal disorders
- CRISPR and Genetic Engineering
- Artificial Intelligence in Healthcare
- Genetic Syndromes and Imprinting
- Bioinformatics and Genomic Networks
Boston Children's Hospital
2020-2024
Broad Institute
2020-2024
Boston Children's Museum
2021-2024
Harvard University
2024
Michigan Medicine
2018-2019
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play major role this disparity. While 13% carry high-risk recessive genotypes, only fraction these individuals develops FSGS or failure, indicating involvement additional disease modifiers. Here, we show that presence p.N264K missense variant, when co-inherited with G2 allele,...
To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations HLA-DR/DQ region, common variants NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved significance were replicated Korean, South Asian African populations. Trans-ethnic meta-analyses including...
Abstract Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association (GWAS). Efforts maximize their accuracy are ongoing. Using 240 glomerular (GLOM) 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we 5371 GLOM 9787 TUBE with at least one variant significantly associated expression (eGene) by incorporating single-nucleus open chromatin...
Significance Statement The absence of high-resolution epigenomic maps key kidney cell types has hampered understanding kidney-specific genome regulation in health and disease. Kidney-associated genetic variants, identified genome-wide association studies, are concentrated accessible chromatin regions containing regulatory DNA elements. authors describe the generation initial characterization paired these gene expression profiles cells from primary human glomerular cortex cultures. By...
APOL1 risk variants are associated with increased of kidney disease in patients African ancestry, but not all individuals the high-risk genotype develop disease. As gene expression correlates closely degree cell injury both and animal models, mechanisms regulating may be critical determinants allele penetrance. The messenger RNA includes Alu elements at 3′ untranslated region that can form a double-stranded structure (Alu-dsRNA) susceptible to posttranscriptional adenosine deaminase acting...
Black Americans are 3-4 times more likely to develop nondiabetic kidney disease than other populations. Exclusively found in people of recent African (AFR) ancestry, risk variants Apolipoprotein L1 (APOL1) termed G1 and G2 contribute significantly this increased susceptibility. Our group others showed that a missense variant APOL1, rs73885316 (p.N264K, "M1"), is remarkably protective against APOL1 when co-inherited with the allele. Since distance between M1 only 367 base pairs, we initially...
ABSTRACT In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise diagnoses therapeutic discoveries, respectively. We previously discovered that variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined intergenic splice product N OS1AP / Nos1ap neighboring C1orf226/Gm7694 which precludes NOS1 binding, is the predominant isoform mammalian kidney...
ABSTRACT Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play major role this disparity. While 13% carry high-risk recessive genotypes, only fraction these individuals develops FSGS or failure, indicating involvement additional modifiers. Here, we show that presence p.N264K missense variant, when co-inherited with G2...
Abstract In genome-wide association studies (GWAS), combining independent case-control cohorts has been successful in increasing power for meta and joint analyses. This success sparked interest extending this strategy to GWAS of rare common diseases using existing cases external controls. However, heterogeneous genotyping data can cause spurious results. To harmonize data, we propose a new method, two-stage imputation (TSIM), where are imputed separately, merged on intersecting high-quality...
Abstract Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association (GWAS). Efforts maximize their accuracy are ongoing. Using 240 glomerular (GLOM) 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we 5,371 GLOM 9,787 TUBE eQTLs by incorporating single-nucleus open chromatin data transcription start site distance as an “integrative prior”...
ABSTRACT Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in HLA Class II region and three additional signals. But genetic architecture of pSSNS, its genetically driven pathobiology, largely unknown. We conducted multi-population GWAS meta-analysis 38,463 participants (2,440 cases) population specific GWAS, discovering twelve significant associations (eight novel)....