As the new year unfolds, it's a time for reflection on some of the most inspirational stories in human genetics last year, and anticipation of what's to come in this area in 2024.

To mark the occasion, our last 2023 episode of the Genetics Podcast featured the inimitable Dr. Veera Rajogopal in a two-part series on the most exciting genetic developments of 2023. Dr. Veera is a physician-scientist who specialises in psychiatric and behavioural genetics. He’s currently working in pharma on new drug targets for psychiatric and neurological diseases through large-scale genetic association studies. His Twitter threads are epic, and if you haven’t checked out his website, GWAS Stories, we highly recommend you do so.

In addition to our podcast, he’s outlined the most notable advancements in human genetics this year here. Below, we’ll recap this progress; we encourage you to check out Dr. Veera's website and listen to the podcast for additional details. 

  • Human genetics in drug development: In 2023, three genes—BCL11A, APOL1, and APOE4—stood out. These genes, long associated with various diseases and traits, continue to evolve in their narratives. For example, BCL11A's journey led to the FDA approval of Casgevy, a groundbreaking CRISPR-based medicine for blood disorders. APOL1's story in kidney disease in African populations continued to unfold, while APOE's role in Alzheimer's disease saw new developments.
  • Rare disease and drug development: Rare diseases inform drug development for more common ones; the intricacies of gene disruption, often illuminated by Mendelian diseases, provide crucial insights into potential drug targets. Last year, the link between BCL11A and sickle cell disease, and the discovery of a genetic cause for a rare muscle disease related to statin use, were particularly striking.
  • Decoding GWAS loci: The challenge of pinpointing causal genes in GWAS loci remains significant. Loci like BCL11A are exceptions in a vast sea of unexplored genetic potential. The story of the FTO locus in obesity is a prime example of this ongoing struggle.
  • Genetic drift and founder populations: From Finngen's insights into Finnish genetics to Puerto Rican studies highlighting novel risk genes, the study of founder populations continues to reveal genetic secrets. These populations offer unique opportunities due to their genetic homogeneity and history of bottleneck events that drastically reduce population size before it grows again (e.g. colonisation, migration, famine, etc.)
  • South Asian stroke genetics and whole genomes: The largest genetic database from South Asia, the Pakistani Genomic Resource, brought to light novel risk factors for stroke, emphasising the importance of including diverse populations in genetic studies.
  • Consanguinity and common diseases: A groundbreaking study on British Pakistanis shed light on the impact of ancestry on the risk of common diseases, highlighting the importance of recessive mutation loads in disease susceptibility.
  • The unsung heroes - rare coding and non-coding variants: The hunt for rare coding variants continues to yield fascinating discoveries, like the new obesity gene BSN. Similarly, the study of non-coding variants, though challenging, is starting to reveal their significant roles in diseases.

As we turn the page on a transformative year in human genetics, the advancements of 2023 set a formidable foundation for future exploration and innovation. The leaps made in understanding the genetic underpinnings of diseases, the progress in drug development, and the increased emphasis on genetic diversity have not only enriched our knowledge but also opened new avenues for precision medicine. The insights from Dr. Veera and others in the field remind us that each discovery, no matter how small, is a step closer to more personalised and effective healthcare solutions.

Looking ahead, the horizon of human genetics is bright with potential. The challenges and complexities of this field continue to inspire a deeper inquiry, promising a future where the integration of genetics into medicine is not just a possibility but a reality. As we embrace 2024, we do so with anticipation for the continued evolution of this important field. 

For details on the stories shared above, please check out Dr. Veera's website. If audio is your medium of choice, even more detail is available through our podcast with Dr. Veera: 

Part 1

Part 2

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