Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource

Ethics statement The institutional review board (IRB) at the Center for Non-Communicable Diseases (CNCD) (IRB: 00007048, IORG0005843 and FWAS00014490) approved the study. This study has also been approved by the National Bioethics Committee for Research Pakistan (reference number NBC-756). All participants gave written informed consent, which includes publication of relevant indirect identifiers. Recruitment Cases and control individuals were recruited in both public and private hospitals across Pakistan. A breakdown of participants is outlined in Supplementary Table 1 . Phenotypes were defined based on confirmed clinical diagnoses established by primary physicians, supported by relevant laboratory investigations and standardized diagnostic criteria. Participants were identified at the time of hospital presentation and enrolled following diagnostic confirmation and written and oral informed consent was obtained. Cases were identified according to predefined inclusion and exclusion criteria. Control individuals were selected from the same hospitals, typically unrelated or distantly related case attendants who met control criteria. To minimize selection bias, enrolment was carried out across both urban and suburban hospitals that also serve surrounding rural populations. …