Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.
Sun D., Richard M., Musani SK., Sung YJ., Winkler TW., Schwander K., Chai JF., Guo X., Kilpeläinen TO., Vojinovic D., Aschard H., Bartz TM., Bielak LF., Brown MR., Chitrala K., Hartwig FP., Horimoto ARVR., Liu Y., Manning AK., Noordam R., Smith AV., Harris SE., Kühnel B., Lyytikäinen L-P., Nolte IM., Rauramaa R., van der Most PJ., Wang R., Ware EB., Weiss S., Wen W., Yanek LR., Arking DE., Arnett DK., Barac A., Boerwinkle E., Broeckel U., Chakravarti A., Chen Y-DI., Cupples LA., Davigulus ML., de Las Fuentes L., de Mutsert R., de Vries PS., Delaney JAC., Roux AVD., Dörr M., Faul JD., Fretts AM., Gallo LC., Grabe HJ., Gu CC., Harris TB., Hartman CCA., Heikkinen S., Ikram MA., Isasi C., Johnson WC., Jonas JB., Kaplan RC., Komulainen P., Krieger JE., Levy D., Lifelines Cohort Study None., Liu J., Lohman K., Luik AI., Martin LW., Meitinger T., Milaneschi Y., O'Connell JR., Palmas WR., Peters A., Peyser PA., Pulkki-Råback L., Raffel LJ., Reiner AP., Rice K., Robinson JG., Rosendaal FR., Schmidt CO., Schreiner PJ., Schwettmann L., Shikany JM., Shu X-O., Sidney S., Sims M., Smith JA., Sotoodehnia N., Strauch K., Tai ES., Taylor K., Uitterlinden AG., van Duijn CM., Waldenberger M., Wee H-L., Wei W-B., Wilson G., Xuan D., Yao J., Zeng D., Zhao W., Zhu X., Zonderman AB., Becker DM., Deary IJ., Gieger C., Lakka TA., Lehtimäki T., North KE., Oldehinkel AJ., Penninx BWJH., Snieder H., Wang Y-X., Weir DR., Zheng W., Evans MK., Gauderman WJ., Gudnason V., Horta BL., Liu C-T., Mook-Kanamori DO., Morrison AC., Pereira AC., Psaty BM., Amin N., Fox ER., Kooperberg C., Sim X., Bierut L., Rotter JI., Kardia SLR., Franceschini N., Rao DC., Fornage M.
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 5 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, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.