Article
Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes.
Science advances - 18 Nov 2022
Nag Abhishek, Dhindsa Ryan S, Mitchell Jonathan, Vasavda Chirag, Harper Andrew R, Vitsios Dimitrios, Ahnmark Andrea, Bilican Bilada, Madeyski-Bengtson Katja, Zarrouki Bader, Zoghbi Anthony W, Wang Quanli, Smith Katherine R, Alegre-Díaz Jesus, Kuri-Morales Pablo, Berumen Jaime, Tapia-Conyer Roberto, Emberson Jonathan, Torres Jason M, Collins Rory, Smith David M, Challis Benjamin, Paul Dirk S, Bohlooly-Y Mohammad, Snowden Mike, Baker David, Fritsche-Danielson Regina, Pangalos Menelas N, Petrovski Slavé
Abstract excerpt
We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in MAP3K15 were 30% less likely to develop diabetes (P = 5.7 × 10-10) and had lower glycosylated hemoglobin (β = -0.14 SD units, P = 1.1 × 10-24). These associations were independent of body mass index, suggesting protection against insulin resistance...
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