Kyle Walsh

Overview:

Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench science with statistical methods to study the neurobiology of glial senescence and gliomagenesis. This research interrogates human genomic and epigenomic profiles to identify both heritable and modifiable factors that contribute to neurologic and physical decline, applying these approaches to studying the shared neurobiology of cognition, glial senescence, and gliomagenesis. The lab has a long history studying telomere maintenance in pre-malignant cells and its role in the development of cancer, most notably glioblastoma.

Positions:

Associate Professor in Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Associate Professor in Pediatrics

Pediatrics, Children's Health Discovery Institute
School of Medicine

Associate Professor in Population Health Sciences

Population Health Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2011

Yale University School of Medicine

Grants:

My Childhood Cancer: Survey Series

Administered By
Neurosurgery
Awarded By
Alex's Lemonade Stand
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to Pediatric Glioma in Individuals and Diverse populations

Administered By
Neurosurgery
Awarded By
University of Southern California
Role
Principal Investigator
Start Date
End Date

The role of rare and common variants in genetic predisposition to medulloblastoma

Administered By
Neurosurgery
Awarded By
Sontag Foundation
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to pediatric Osteosarcoma and Interaction with Measures of Childhood Growth

Administered By
Neurosurgery
Awarded By
Alex's Lemonade Stand
Role
Principal Investigator
Start Date
End Date

Immune Correlates and Mechanisms of Perinatal Cytomegalovirus Infection and Later Life ALL Development

Administered By
Pediatrics, Children's Health Discovery Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.

The COVID-19 pandemic has produced broad clinical manifestations, from asymptomatic infection to hospitalization and death. Despite progress from genomic and clinical epidemiology research, risk factors for developing severe COVID-19 are incompletely understood and identification of modifiable risk factors is desperately needed. We conducted linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait genetic correlation between COVID-19 severity and various polygenic phenotypes. To attenuate the genetic contribution of smoking and BMI, we further conducted sensitivity analyses by pruning genomic regions associated with smoking/BMI and repeating LDSR analyses. We identified robust positive associations between the genetic architecture of severe COVID-19 and both BMI and smoking. We observed strong positive genetic correlation (rg) with diabetes (rg = 0.25) and shortness of breath walking on level ground (rg = 0.28) and novel protective associations with vitamin E (rg = - 0.53), calcium (rg = - 0.33), retinol (rg = - 0.59), Apolipoprotein A (rg = - 0.13), and HDL (rg = - 0.17), but no association with vitamin D (rg = - 0.02). Removing genomic regions associated with smoking and BMI generally attenuated the associations, but the associations with nutrient biomarkers persisted. This study provides a comprehensive assessment of the shared genetic architecture of COVID-19 severity and numerous clinical/physiologic parameters. Associations with blood and plasma-derived traits identified biomarkers for Mendelian randomization studies to explore causality and nominates therapeutic targets for clinical evaluation.
Authors
Byun, J; Han, Y; Walsh, KM; Park, AS; Bondy, ML; Amos, CI
MLA Citation
Byun, Jinyoung, et al. “Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.Sci Rep, vol. 12, no. 1, Feb. 2022, p. 1891. Pubmed, doi:10.1038/s41598-022-05832-5.
URI
https://scholars.duke.edu/individual/pub1510173
PMID
35115602
Source
pubmed
Published In
Scientific Reports
Volume
12
Published Date
Start Page
1891
DOI
10.1038/s41598-022-05832-5

Long telomeres in need of a SNP: Germline contributions of telomere maintenance to glioma.

Authors
Kachuri, L; Walsh, KM
MLA Citation
Kachuri, Linda, and Kyle M. Walsh. “Long telomeres in need of a SNP: Germline contributions of telomere maintenance to glioma.Neuro Oncol, vol. 24, no. 2, Feb. 2022, pp. 182–83. Pubmed, doi:10.1093/neuonc/noab260.
URI
https://scholars.duke.edu/individual/pub1510174
PMID
34758087
Source
pubmed
Published In
Neuro Oncol
Volume
24
Published Date
Start Page
182
End Page
183
DOI
10.1093/neuonc/noab260

An integrated genome and phenome-wide association study approach to understanding Alzheimer’s disease predisposition

Authors
Khaire, AS; Wimberly, CE; Semmes, EC; Hurst, JH; Walsh, KM
MLA Citation
Khaire, Archita S., et al. “An integrated genome and phenome-wide association study approach to understanding Alzheimer’s disease predisposition.” Cold Spring Harbor Laboratory. Crossref, doi:10.1101/2022.01.03.22268705.
URI
https://scholars.duke.edu/individual/pub1505923
Source
crossref
DOI
10.1101/2022.01.03.22268705

Insurance status as a mediator of clinical presentation, type of intervention, and short-term outcomes for patients with metastatic spine disease.

BACKGROUND: It is well established that insurance status is a mediator of disease management, treatment course, and clinical outcomes in cancer patients. Our study assessed differences in clinical presentation, treatment course, mortality rates, and in-hospital complications for patients admitted to the hospital with late-stage cancer - specifically, metastatic spine disease (MSD), by insurance status. METHODS: The United States National Inpatient Sample (NIS) database (2012-2014) was queried to identify patients with visceral metastases, metastatic spinal cord compression (MSCC) or pathological fracture of the spine in the setting of cancer. Clinical presentation, type of intervention, mortality rates, and in-hospital complications were compared amongst patients by insurance coverage (Medicare, Medicaid, commercial or unknown). Multivariable logistical regression and age sensitivity analyses were performed. RESULTS: A total of 48,560 MSD patients were identified. Patients with Medicaid coverage presented with significantly higher rates of MSCC (p < 0.001), paralysis (0.008), and visceral metastases (p < 0.001). Patients with commercial insurance were more likely to receive surgical intervention (OR 1.43; p < 0.001). Patients with Medicaid < 65 had higher rates of prolonged length of stay (PLOS) (OR 1.26; 95% CI, 1.01-1.55; p = 0.040) while both Medicare and Medicaid patients < 65 were more likely to have non-routine discharges. In-hospital mortality rates were significantly higher for patients with Medicaid (OR 2.66; 95% CI 1.20-5.89; p = 0.016) and commercial insurance (OR 1.58; 95% CI 1.09-2.27;p = 0.013) older than 65. CONCLUSION: Given the differing severity in MSD presentation, mortality rates, and rates of PLOS by insurance status, our results identify disparities based on insurance coverage.
Authors
Price, MJ; De la Garza Ramos, R; Dalton, T; McCray, E; Pennington, Z; Erickson, M; Walsh, KM; Yassari, R; Sciubba, DM; Goodwin, AN; Goodwin, CR
MLA Citation
Price, Meghan J., et al. “Insurance status as a mediator of clinical presentation, type of intervention, and short-term outcomes for patients with metastatic spine disease.Cancer Epidemiol, vol. 76, Feb. 2022, p. 102073. Pubmed, doi:10.1016/j.canep.2021.102073.
URI
https://scholars.duke.edu/individual/pub1506926
PMID
34857485
Source
pubmed
Published In
Cancer Epidemiol
Volume
76
Published Date
Start Page
102073
DOI
10.1016/j.canep.2021.102073

Mitochondrial 1555 G&gt;A variant as a potential risk factor for childhood glioblastoma

Background: Childhood glioblastoma multiforme (GBM) is a highly aggressive disease with low survival, and its etiology, especially concerning germline genetic risk, is poorly understood. Mitochondria play a key role in putative tumorigenic processes relating to cellular oxidative metabolism, and mitochondrial DNA variants were not previously assessed for association with pediatric brain tumor risk. Methods: We conducted an analysis of 675 mitochondrial DNA variants in 90 childhood GBM cases and 2789 controls to identify enrichment of mitochondrial variant associated with GBM risk. We also performed this analysis for other glioma subtypes including pilocytic astrocytoma. Nuclear-encoded mitochondrial gene variants were also analyzed. Results: We identified m1555 A>G was significantly associated with GBM risk (adjusted OR 29.30, 95% CI 5.25-163.4, P-value 9.5 X 10-4). No association was detected for other subtypes. Haplotype analysis further supported the independent risk contributed by m1555 G>A, instead of a haplogroup joint effect. Nuclear-encoded mitochondrial gene variants identified significant associations in European (rs62036057 in WWOX, adjusted OR = 2.99, 95% CI 1.88-4.75, P-value = 3.42 X 10-6) and Hispanic (rs111709726 in EFHD1, adjusted OR = 3.57, 95% CI 1.99-6.40, P-value = 1.41 X 10-6) populations in ethnicity-stratified analyses. Conclusion: We report for the first time a potential role played by a functional mitochondrial ribosomal RNA variant in childhood GBM risk, and a potential role for both mitochondrial and nuclear-mitochondrial DNA polymorphisms in GBM tumorigenesis. These data implicate cellular oxidative metabolic capacity as a contributor to the etiology of pediatric glioblastoma.
Authors
Li, S; Gai, X; Myint, SS; Arroyo, K; Morimoto, L; Metayer, C; De Smith, AJ; Walsh, KM; Wiemels, JL
MLA Citation
Li, S., et al. “Mitochondrial 1555 G>A variant as a potential risk factor for childhood glioblastoma.” Neuro Oncology Advances, vol. 4, no. 1, Jan. 2022. Scopus, doi:10.1093/noajnl/vdac045.
URI
https://scholars.duke.edu/individual/pub1532468
Source
scopus
Published In
Neuro Oncology Advances
Volume
4
Published Date
DOI
10.1093/noajnl/vdac045

Research Areas:

Muser Mentor