Loading Events

Works-in-Progress Seminar Series

October 27 @ 1:00 pm - 2:00 pm

Works-in-Progress Seminar

Presented by the Department of Epidemiology

Talk title:Low Generalizability of Polygenic Risk Scores in African Populations

Speaker: Lerato Majara
Global Initiative for Neuropsychiatric Genetics in Research (GINGER) Fellow
University of Cape Tow

Abstract:

African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRS) in simulations across Africa and in empirical data from South Africa, Uganda, and the UK to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South Africans, we find that PRS accuracy is low for all traits but varies across groups. Differences in African ancestries contribute more to variability in PRS accuracy than other large cohort differences considered between individuals in the UK versus Uganda. We computed PRS in African ancestry populations using existing European-only versus ancestrally diverse genetic studies; the increased diversity produced the largest accuracy gains for hemoglobin concentration and white blood cell count, reflecting large-effect ancestry-enriched variants in genes known to influence sickle cell anemia and the allergic response, respectively. Differences in PRS accuracy across African ancestries originating from diverse regions are as large as across out-of-Africa continental ancestries, requiring commensurate nuance.

Talk title: Can Exposure to Infections Determine the Outcomes or Phenotypes of Epilepsy?

Speaker: Symon Kariuki
Global Initiative for Neuropsychiatric Genetics in Research (GINGER) Fellow
KEMRI-Wellcome Trust Institute in Kilifi, Kenya

Abstract:

Infections of the central nervous system (CNS) contribute considerably to the burden of epilepsy in LMICs, but the nature and presentation of epilepsy following these infections is not fully understood. We examined if epilepsy foutcomes are associated with the exposure to parasitic infections, using a case-comparison study nested in a cross-sectional survey of people with active convulsive epilepsy. Multiplicative and additive scale (RERI) interactions were explored to determine the effect of co-infections on epilepsy features. found that parasitic infections that infect the CNS are not only associated with epilepsy, but also determine the occurrence of features and phenotypes of epilepsy. In children with epilepsy, exposure to infections is particularly associated with convulsive status epilepticus, neurological deficits and intellectual disability, while in adults it is associated with frequent seizures. Individual infections may increase some features (e.g. falciparum malaria increasing risk for convulsive status epilepticus) but not others. In conclusion, control of infections may reduce the risk of epilepsy becoming severe in addition to preventing epilepsy directly caused by infections in the community.

Details

Date:
October 27
Time:
1:00 pm - 2:00 pm
Calendar(s):
Public Events, School-wide Events, University-wide Events
Event type(s):
Lectures / Seminars / Forums
Website:
https://www.hsph.harvard.edu/epidemiology/epi-seminar-series/
Registration:
https://harvard.zoom.us/meeting/register/tJwqf-morDoqHtLiHytzI9aTJFekyh3xkxDe