Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. 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 symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 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 and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
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This project was largely supported by grant R01HL118305 from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, with additional support from R01HL105756. A full set of study-specific funding sources and acknowledgments is provided in the Supplemental subjects and methods.
The summary statistics of the meta-analyses generated in this project are available at the CHARGE Consortium Summary Results at the database of Genotypes and Phenotypes (dbGaP) under accession number dbGaP: phs000930 or directly from the authors upon request.
Sun, Daokun; Richard, Melissa A.; Musani, Soloman K.; Sung, Yun Ju; Winkler, Thomas W.; Schwander, Karen; Chai, Jin Fang; Guo, Xiuqing; Kilpeläinen, Tuomas O.; Vojinovic, Dina; Aschard, Hugues; Bartz, Traci M.; Bielak, Lawrence F.; Brown, Michael R.; Chitrala, Kumaraswamy; Hartwig, Fernando P.; Horimoto, Andrea R. V. R.; Liu, Yongmei; Manning, Alisa K.; Noordam, Raymond; and Arnett, Donna K., "Multi-Ancestry Genome-Wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits" (2020). Epidemiology Faculty Publications. 78.
Document S1. Supplemental subjects and methods, supplemental acknowledgments, and Figures S1–S12.
1-s2.0-S2666247720300130-mmc2.xlsx (5767 kB)
Document S2. Tables S1–S16.
1-s2.0-S2666247720300130-mmc3.pdf (3779 kB)
Document S3. Article plus supplemental information.