The relationship between retinal arteriolar and venular calibers is genetically mediated, and each is associated with risk of cardiovascular disease.

PURPOSE: Retinal arteriolar and venular calibers are highly heritable and associated with cardiovascular disease. This study was designed to investigate the relative influence of genetic and environmental factors on the high phenotypic correlation (r = 0.59) between these two traits and to assess the shared and specific influence of established and novel cardiovascular disease risk factors on them. METHODS: A total of 1463 Caucasian female twins (706 monozygotic and 757 dizygotic), between 24 and 79 years of age, underwent retinal photography from which retinal arteriolar (mean, 153.75 ± 22.1 µm, SD) and venular (mean, 232.1 ± 36.6 µm) calibers were measured with semiautomated software. A bivariate heritability model was used to assess the genetic and environmental influences underlying both specific trait variance and the covariance between the vessel traits. The investigation was an assessment of phenotypic associations between retinal arteriolar and venular calibers and cardiovascular disease risk factors. RESULTS: Additive genetic factors accounted for approximately three fourths of the covariance between retinal arteriolar and venular calibers within the cohort. This finding was replicated in a sample of 1981 twins from the Australian Twins Eye Study. The partial correlation showed that known risk factors accounted for only 5% of the covariance between arteriolar and venular calibers. Novel associations were found between venular caliber and ß-cell function (P = 0.011) and insulin sensitivity (P = 0.002). CONCLUSIONS: These results suggest that future gene-mapping studies may identify pleiotropic genetic variants influencing both retinal arteriolar and venular calibers. Genetic variants associated with retinal caliber and (risk factors for) cardiovascular disease should provide new etiologic insights into this complex disease.

Direction of causation modeling between cross-sectional measures of parenting and psychological distress in female twins.

Under certain conditions, cross-sectional analysis of cross-twin intertrait correlations can provide important information about the direction of causation (DOC) between two variables. A community-based sample of Australian female twins aged 18 to 45 years was mailed an extensive Health and Lifestyle Questionnaire (HLQ) that covered a wide range of personality and behavioral measures. Included were self-report measures of recent psychological distress and perceived childhood environment (PBI). Factor analysis of the PBI yielded three interpretable dimensions: Coldness, Overprotection, and Autonomy. Univariate analysis revealed that parental Overprotection and Autonomy were best explained by additive genetic, shared, and nonshared environmental effects (ACE), whereas the best-fitting model for PBI Coldness and the three measures of psychological distress (Depression, Phobic Anxiety, and Somatic Distress) included only additive genetic and nonshared environmental effects (AE). A common pathway model best explained the covariation between (1) the three PBI dimensions and (2) the three measures of psychological distress. DOC modeling between latent constructs of parenting and psychological distress revealed that a model which specified recollected parental behavior as the cause of psychological distress provided a better fit than a model which specified psychological distress as the cause of recollected parental behavior. Power analyses and limitations of the findings are discussed.