RESUMO
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.
RESUMO
OBJECTIVE: A strong genetic predisposition for type 2 diabetes mellitus (T2DM) may aggravate the negative effects of low socioeconomic position (SEP) in the etiology of the disorder. This study aimed to examine cross-sectional and longitudinal associations and interactions of a genetic risk score (GRS) and SEP with T2DM and to investigate whether clinical and behavioral risk factors can explain these associations and interactions. METHODS: We used data from 13,027 genotyped participants from the Lifelines study. The GRS was based on single-nucleotide polymorphisms genome-wide associated with T2DM and was categorized into tertiles. SEP was measured as educational level. T2DM was based on biological markers, recorded medication use, and self-reports. Cross-sectional and longitudinal associations and interactions between the GRS and SEP on T2DM were examined. RESULTS: The combination of a high GRS and low SEP had the strongest association with T2DM in cross-sectional (odds ratio = 3.84, 95% confidence interval = 2.28-6.46) and longitudinal analyses (hazard ratio = 2.71, 1.39-5.27), compared with a low GRS and high SEP. Interaction between a high GRS and a low SEP was observed in cross-sectional (relative excess risk due to interaction = 1.85, 0.65-3.05) but not in longitudinal analyses. Clinical and behavioral risk factors mostly explained the observed associations and interactions. CONCLUSIONS: A high GRS combined with a low SEP provides the highest risk for T2DM. These factors also exacerbated each other's impact cross-sectionally but not longitudinally. Preventive measures should target individual and contextual factors of this high-risk group to reduce the risk of T2DM.