EP 130: Quarterly insights into noncoding variants and GWAS with Dr. Veera Rajagopal
Apr 11, 2024
auto_awesome
Dr. Veera Rajagopal discusses insights into noncoding variants and GWAS, highlighting polydactyl mutations, low-affinity TF binding, lncRNA roles in NDD, CHD2 deletion, Brugada syndrome in SE Asians, and future of GWAS studies on type 2 diabetes.
Understanding the importance of low-affinity binding in transcription factor interactions for drug discovery.
Identification of a non-coding variant associated with Nathan's Syndrome in Southeast Asian populations.
Clustering genome-wide variants for type 2 diabetes reveals pathway-specific risks based on genetic ancestries.
Deep dives
Exploring Non-Coding Variants in Rare Diseases
Recent studies have delved into the significance of non-coding variants in rare diseases, particularly focusing on the mechanisms of transcription factor binding. Through research on an enhancer called ZRS enhancer and its impact on limb development, insights were gained into the complexities of transcription factor binding and tissue-specific gene expression, shedding light on the intricacies of developmental anomalies.
Discovery of Non-Coding Variant in Neurodevelopmental Disorders
A groundbreaking discovery identified a non-coding variant linked to a neurodevelopmental disorder known as Nathan's Syndrome, uncovering a deletion of a long non-coding RNA called Chaser. This variant, specific to Southeast Asian populations, demonstrated a significant role in the disease etiology, providing a unique glimpse into genetic influences on the disorder.
Clustering Genome-Wide Variants for Disease Insights
In an innovative approach, researchers clustered genome-wide variants associated with type 2 diabetes based on distinct disease mechanisms, revealing clusters such as lipodystrophy that have differential impacts across genetic ancestries. This novel methodology offers insights into pathway-specific disease risks and envision a future of precision medicine based on individual genetic makeup rather than self-reported ancestry.
Pathway-Specific Analysis in Genome-Wide Association Studies
Advancements in genome-wide association studies have highlighted the importance of pathway-specific analysis to dissect disease heterogeneity and unravel unique genetic architectures underlying varied phenotypic presentations. By stratifying individuals based on pathway-specific risk scores, researchers aim to refine disease risk assessments and tailor interventions based on the individual's genetic predispositions.
Implications of GWAS Clusters in Precision Medicine
The utilization of GWAS clusters to identify pathway-specific genetic variants holds significant implications for precision medicine, particularly in tailoring interventions based on genetic ancestry and pathway-specific risks. These findings not only enhance disease stratification but also guide drug development and clinical trial designs to address ancestry-specific genetic predispositions more effectively.
Join us as we welcome back Dr. Veera Rajagopal, a discovery scientist at Regeneron with an interest in human genetics and drug target discovery in neuroscience and psychiatry. If you’re a regular listener of The Genetics Podcast, you are likely familiar with Dr. Veera’s annual round-up episodes. This year, we are excited to announce quarterly episodes with Dr. Veera, where he and Patrick walk you through the latest developments in genetics, drug discovery, and precision medicine throughout the year. This quarter’s episode will focus on non-coding variants and the future of genome-wide association studies (GWAS). Tune in now, and don’t forget to check out Veera’s substack, GWAS Stories, and his Twitter, @doctorveera.
Remember Everything You Learn from Podcasts
Save insights instantly, chat with episodes, and build lasting knowledge - all powered by AI.
