CitationWilliams, Redford; Brummett, Beverly H.; & Siegler, Ilene C. (2010). How do genes, environmental stressors, and their interactions get inside the body to increase disease risk in Add Health participants at Wave IV (and thereafter)?. 2010 Add Health Users Conference. Bethesda, MD.
AbstractGenes, environmental stressors, and their interactions can only influence the development of medical disorders via effects on psychosocial, behavioral and biological characteristics (endophenotypes) that are directly involved in ethiology and pathogenesis. Lower socioeconomic status (SES) is one environmental factor that has been shown to have profound effects on risk of cardiovascular disease (CVD). Using Wave IV biomarker data, we have been able to replicate (p < 0.0001) an earlier finding in a French cohort that one’s educational level is inversely associated with systolic blood pressure (SBM). This association was largely accounted for by BMI, race/ethnicity,gender, marital status and lifestyle characteristics (physical activity, alcohol consumption and smoking). Our prior research has identified several genetic variants that are also associated with pre-disease endophenotypes. The more active allele (L) of a serotonin transporter promoter polymorphism (5HTTLPR) is associated with increased SBP reactivity to acute stress in both men and women, blacks and whites. In comparison to women carrying the 5HTTLPR L allele and exposed to high or low stress life situations, women who are homozygous for the less active allele (SS) and exposed to high stress have higher levels of depressive symptoms (a risk factor for CVD), but those in low stress situations have lower depressive symptom levels. Among men, it is those with the 5HTTLPR L allele who have high depressive symptom levels in stressful life situations. A single nucleotide polymorphism (SNP) on the APOE gene is associated with an adverse lipid profile in persons exposed to a high live stress situation, but with a more positive profile in those not so exposed. A functional SNP on the 5HT2C serotonin receptor gene is robustly associated in men with larger cortisol responses to acute mental stress. It will be possible, in our ongoing investigations using Add Health Wave IV data, to both replicate these associations and determine whether these same genetic variants influence the development of major medical disorders. Is, for example, the incidence of hypertension significantly higher among those with low education levels who also carry the 5HTTLPR L allele? Is the 5HTTLPR SS genotype associated with increased depression among women exposed to stressful life situations, but with decreased depressive symptoms in those not so exposed? Is the LL genotype associated with increased depression in men exposed to chronic stress? Is the APOE SNP we find associated with bad and good lipid profiles in persons exposed to high vs normal stress life situations also associated with similar profiles in Wave IV participants, depending on stress exposure? And is the 5HTR2C SNP we find associated with larger cortisol responses to acute mental stress in men also associated with disorders like type 2 diabetes, central obesity and hypertension whose pathogenesis is increased by chronic cortisol excess?
Reference TypeConference proceeding
Book Title2010 Add Health Users Conference
Brummett, Beverly H.
Siegler, Ilene C.