EP 167: Research Roundup with Dr. Veera: Wrapping up 2024 in four pioneering papers

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, you may be familiar with Veera’s quarterly appearances on the show, where Patrick and he discuss the latest developments in genetics, drug discovery, and precision medicine. Grab yourself a cup of something warm and tune in as Veera and Patrick close out 2024 with a wrap up covering: Population genomics programs New Alzheimer’s research The impact of genetics on menopause onset Newborn genetic screening Tune in now, and don’t forget to check out Veera’s substack, GWAS Stories, and his Twitter, @doctorveera.

00:00 Intro to The Genetics Podcast

01:00 Welcome back to Veera and topics to be covered

03:50 Insights into the causes and consequences of DNA repeat expansions from 700,000 biobank participants, including:

Focusing on recent findings related to Huntington’s HTT repeat expansion in striatal neurons
Leveraging newly-sequenced GWAS data from the UK Biobank and All of Us cohorts to study short tandem repeats (STRs), particularly the CAG triplet repeat
Identifying multiple participants with expanded repeats exceeding 45 base pairs, revealing that three genetic sites account for over 97% of these expansions
Exploring factors that may prevent or impact the phenotypic manifestation of repeat expansions
Read the paper

30:51 The impact of lipids in protecting against pathogenic APOE and Alzheimer’s disease (AD)

Investigating how different haplotypes interact with low-density lipoprotein receptors in neuronal tissues, influencing cholesterol lipid transport and AD risk
Examining lipid profiles in APOE carriers, including elevated low-density lipoprotein cholesterol levels in APOE4 carriers and decreased levels in APOE2 carriers, and their effects on cholesterol and nutrient supply to neurons
Exploring gene therapy approaches for delivering APOE2 into the brain
Read the paper

44:20 How low frequency genetic variants can impact the age of menopause onset

Exploring the relationship between age of menopause and ovarian function
Addressing the challenges in studying recessive genetic associations
Examining how homozygosity of a variant in the CCDC201 gene influences primary ovarian insufficiency and strongly associates with early menopause
Read the paper

57:58 GUARDIAN: Expanding screening for newborns to include targeted genome sequencing

Examining the 72% participation rate among invited families and the 90% consent rate for expanded panel screening
Exploring opportunities for early treatment and preventive interventions
Ensuring databases are representative across diverse populations
Tune into Episode 117 to hear from the leader of the GUARDIAN program, Wendy Chung

01:11:54 Predictions for 2025 and closing remarks!