⚖️ Why is this important? South Asians contribute >30% of global T2D burden while being represented by 0.4% of genetic studies of T2D. If precision medicine is to be delivered equitably and effectively, we need to improve representation.

This work was supported by a fantastic partnership between our Genes & Health volunteers, team, researchers and Life Sciences consortium. Thank you to all involved.

🧬 >54,000 whole exome sequences in South Asians from a single study: @genesandhealth.bsky.social @qmul-wiph.bsky.social @blizardinstitute.bsky.social, @qmul-ceg.bsky.social PHURI @qminnovation.bsky.social. We validated our findings with data from Dr.Mohan's Diabetes Specialities Centre

💊 🧬 Our novel findings have the power to inform drug discovery and precision medicine and ensure equity.

and major thanks to @commsmed.nature.com a fabulous multidisciplinary journal and perfect home for this kind of interdisciplinary research.

Major thanks to data contributors: @genesandhealth.bsky.social Madras Diabetes Research Foundation, SHARE, Scotland. And to study participants and co-authors (many not yet on bluesky!) @theodyssee.bsky.social @anavinuela.bsky.social @arnsbr.bsky.social

We also observed that for people with this genetic risk, certain therapies e.g. sulfonylureas worsened glycemic control because of their mechanism of action. No difference for those in GLP-1RA therapies.

Per XBP1 risk allele carried: HbA1c at dx was 4.32 mmol/mol higher and in people with young+lean onset T2D, this was 6.41 mmol/mol. Meaning that homozygous risk allele carriers have between 8-12 mmol/mol higher HbA1c.

🔍 Using variety of data types (clinical, genomic, transcriptomics and pharmacogenomics) we show how South and East Asians carry higher risk of lower cell-type specific XBP1 expression which likely leads to early beta-cell death, causing worse HbA1c control in young and lean onset T2D.

🎯 XBP1 is a well-known transcription factor, with loads of in vitro and in vivo evidence of its role in maintaining beta-cell health under metabolically stressful conditions.

🧬 We know that early onset beta-cell dysfunction is a key pathway for young + lean type 2 diabetes, but we lack vast genomic resources in which to study the underlying biology.

🤣🤣

stop making plots!!! 😅