LAUSR

Background: Genome-wide association studies (GWAS) have identified hundreds of genetic loci for blood pressure (BP) traits and advanced our understanding of BP regulation and hypertension etiology. Psychological and social factors are known to influence BP and risk of cardiovascular diseases. Accounting for psychosocial factors may help identify BP loci and extend our knowledge of its genetic architecture. Methods: To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptomatology, trait anxiety, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. Results: In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response ( PLCL2 ), synaptic function and neurotransmission ( LIN7A, PFIA2 ), as well as genes previously implicated in neuropsychiatric or stress-related disorders ( FSTL5, CHODL ). Conclusion: These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.