Cell-type-resolved genetic variation shapes inflammatory bowel disease risk

Patient recruitment and single-cell sequencing This study was approved by the National Health Service (NHS) Research Ethics Committee (Cambridge South, REC ID 17/EE/0338). Written informed consent was given by all participants. 296 individuals without IBD and 125 individuals with CD were recruited at Addenbrooke’s Hospital, Cambridge, UK. Patients with CD were required to have a history of ileal disease involvement. During routine endoscopy, gastrointestinal biopsies were collected from the rectum and terminal ileum, and blood samples were drawn after the procedure. Terminal ileal biopsies were obtained from 243 individuals without IBD and 119 individuals with CD. Ileal biopsies from patients with CD included both inflamed and uninflamed tissue. Rectal biopsies were collected from 275 individuals without IBD. Where possible, rectal and ileal samples were collected from the same healthy individuals, and blood and ileal samples were collected from the same patients. For gastrointestinal biopsies, we have developed a gentle single-cell dissociation protocol that minimizes transcriptional changes and cell stress or death during cell isolation. Early samples were processed using version 1 of the protocol, whereas most of the samples were processed using version 2 90 , 91 . Whole blood was collected for scRNA-seq from 95 individuals with CD. …