Dr. Spencer Nadolsky and Karl sit down with Dr. Adam Auton, geneticist at 23andMe, to break down a brand new paper using data from over 27,000 people that identified specific genetic variants linked to how well GLP-1 medications work and how likely someone is to experience side effects. 23andMe has over 11 million people in their research database and used voluntary survey data on medication use, dosage, duration, weight loss, and side effects to match against genetic profiles at scale, making this one of the most powerful datasets anyone has brought to this question.

In this episode they cover how genome-wide association studies work and why scanning 600,000 genetic variants at once lets researchers find signals they never could have predicted in advance, why the first signal that jumped out of the data was a variant right in the GLP-1 receptor itself and why that was the moment the team knew they were on the right track, why the same variant that predicts better efficacy also predicts a higher risk of side effects and what that tells us about how the drug is being processed, why tirzepatide users showed a separate signal in the GIP receptor that modulates side effects rather than weight loss, why carrying both variants could make someone 14 times more likely to experience side effects on tirzepatide, why genetics explains roughly 10 percent of weight loss variation and what the other 90 percent looks like, why women tend to respond better than men and why diabetics tend to respond less well, what the future of this research looks like including who regains weight after stopping and whether those patterns are genetically predictable, and why heritability is a statistical measure that gets badly misunderstood even by clinicians.

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