Genome-wide association study highlights 44 loci for transient ischemic attack and shared genetic architecture with stroke

Transient ischemic attack (TIA) is a critical harbinger of subsequent stroke, and most genetic risk remains uncharacterized. Here we firstly performed the largest TIA genome-wide association study (GWAS) meta analysis in 1,332,453 European individuals (58,976 cases and 1,273,477 controls), followed by an independent replication in 610,409 non-European individuals (23,557 TIA and 586,852 controls), a multi-ancestry GWAS meta analysis in 1,942,862 individuals (82,533 cases and 1,860,329 controls), and a cross-trait GWAS meta-analysis of TIA with stroke and its subtypes. We identified 44 loci including 25 known stroke loci and 19 TIA specific loci (CELSR2, SLC4A7, CASC15, SRRM3, SLC44A1, LOC107984361, GSE1, LOC105372530, HCG20, OXR1, SLC4A1, RBBP8, TUSC3, DCC, PALMD, ZNF475, CTAGE1, FUT2 and MRPS6). Post-GWAS pinpointed 51 high confidence genes (24 are potential therapeutic targets) and 13 statistically significant pathways including protein-lipid complex, neurofibrillary tangle, high-density lipoprotein particle. These findings provide critical insights into the genetic basis of TIA.