Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease

• DOI: 10.1016/j.xcrm.2023.101155
• Publication Date: 2023-08-15T15:08:39Z
• Authors: Ruth Hanssen; Chiara Auwerx; Maarja Jõeloo; Marie C. Sadler; Elana Henning; Julia Keogh; Rebecca Bounds; Miriam Smith; Helen V. Firth; Zoltán Kutalik; I. Sadaf Farooqi; Alexandre Reymond; Katherine Lawler
• Keywords: Mendelian Randomization

New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2 (breakpoint 2-3 [BP2-3]) encompassing SH2B1, mediator of leptin insulin signaling. Phenome-wide association scans in the UK (N = 502,399) Estonian 208,360) biobanks show that carriers have increased body mass index (BMI; p 1.3 × 10