Polygenic Epidemiology

Much of the genetic basis of complex traits is present on current genotyping products, but the individual variants that affect the traits have largely not been identified. Several traditional problems in genetic epidemiology have recently been addressed by assuming a polygenic basis for disease and treating it as a single entity. Here I briefly review some of these applications, which collectively may be termed polygenic epidemiology. Methodologies in this area include polygenic scoring, linear mixed models, and linkage disequilibrium scoring. They have been used to establish a polygenic effect, estimate genetic correlation between traits, estimate how many variants affect a trait, stratify cases into subphenotypes, predict individual disease risks, and infer causal effects using Mendelian randomization. Polygenic epidemiology will continue to yield useful applications even while much of the specific variation underlying complex traits remains undiscovered.     

维吾尔族人体身高遗传度的首次研究

本文是对新疆地区维吾尔族人体身高遗传度的首次研究,通过对新疆319名青年的调查分析测得维吾尔族人体身高的点估计值为48.72％;并通过多元回归法分析得知在新疆环境因素中地区的差异对身高无显著影响。     

The Hawaii family study of cognition: A reply

Differences in age and number of children tested per family between two ethnic groups (Americans of Japanese ancestry and Americans of European ancestry) have a trivial effect on differences in regressions of midchild on midparent for tests of specific cognitive abilities. Although the regression of offspring on midparent value is not a mathematical function of the spouse correlation, an empirical association between these two measures of familial resemblance is expected for characters with nonzero heritability. Such an association is reported for anthropometric characters. Since age effects contribute to the covariance of family members, age correction of family cognitive data is essential.The results reported here are made possible by collaboration of a group of investigators (G. C. Ashton, R. C. Johnson, M. P. Mi, and M. N. Rashad at the University of Hawaii, and J. C. DeFries, G. E. McClearn, S. G. Vandenberg, and J. R. Wilson at the University of Colorado) supported by NSF Grant GB-34720 and Grant HD-06669 from the National Institute of Child Health and Human Development.     

Generalized anxiety disorder and anorexia nervosa: evidence of shared genetic variation

Background: Previous studies have indicated a high prevalence of generalized anxiety disorder (GAD) in women with anorexia nervosa (AN). However, the shared genetic and environmental components of these disorders have not been explored. This study seeks to elucidate the shared genetic and environmental components between GAD and AN. Method: Using 2,083 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, structural equation modeling was used to obtain maximum likelihood estimates of the environmental genetic, shared and unique environmental components in 496 women with GAD, 47 women with AN, 43 women with GAD + AN, and 1,497 women without GAD or AN. Results: Results show that the heritability of GAD was 0.32 and AN was 0.31, and the genetic correlation between the two disorders was 0.20, indicating a modest genetic contribution to their comorbidity. Unique environment estimate was 0.68 for GAD and 0.69 for AN, with a unique environmental correlation of 0.18. All common environmental parameters were estimated at zero. Conclusions: The modest shared genetic and unique environmental liability to both disorders may help explain the high prevalence of GAD in women with AN. This knowledge could help in the treatment and prevention of comorbid disorders. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Depression and obesity: do shared genes explain the relationship?

Background: Studies have found a modest association between depression and obesity, especially in women. Given the substantial genetic contribution to both depression and obesity, we sought to determine whether shared genetic influences are responsible for the association between these two conditions. Methods: Data were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are members of the community‐based University of Washington Twin Registry. The presence of depression was determined by self‐report of doctor‐diagnosed depression. Obesity was defined as body mass index of ≥30 kg/m², based on self‐reported height and weight. Generalized estimating regression models were used to assess the age‐adjusted association between depression and obesity. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. Results: We found a modest phenotypic association between depression and obesity (odds ratio=1.6, 95% confidence interval=1.2–2.1). Additive genetic effects contributed substantially to depression (57%) and obesity (81%). The best‐fitting bivariate model indicated that 12% of the genetic component of depression is shared with obesity. Conclusions: The association between depression and obesity in women may be in part due to shared genetic risk for both conditions. Future studies should examine the genetic, environmental, social, and cultural mechanisms underlying the relationship between this association. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Genetics of hemostasis: differential effects of heritability and household components influencing lipid concentrations and clotting factor levels in 282 pediatric stroke families

BACKGROUND: The identification of heritable and environmental factors possibly influencing a condition at risk should be a prerequisite for the search for the proportion of variance attributable for shared environmental effects (c(2)) modulating the risk of disease. Such epidemiologic approaches in families with a first acute ischemic stroke during early childhood are lacking. OBJECTIVES: Our goal was to estimate the phenotypic variation within lipid concentrations and coagulation factor levels and to estimate the proportions attributable to heritability (h(2)r) and c(2) in pediatric stroke families. METHODS: Blood samples were collected from 1,002 individuals from 282 white stroke pedigrees. We estimated h(2)r and c(2) for lipoprotein (a) [Lp(a)], cholesterol, high-density lipoprotein, low-density lipoprotein (LDL), fibrinogen, factor (F) II, FV, FVIIIC, von Willebrand factor (vWF), antithrombin, protein C, protein S, plasminogen, protein Z, total tissue factor pathway inhibitor (TFPI), prothrombin fragment F1.2, and D-dimer, using the variance component method in sequential oligogenetic linkage analysis routines. RESULTS: When incorporating h(2)r and c(2) in one model adjusted for age, blood group, sex, smoking, and hormonal contraceptives, significant h(2)r estimates were found for Lp(a), LDL, fibrinogen, protein C, and protein Z. In addition to the significant h(2)r estimates, c(2) showed a significant effect on phenotypic variation for fibrinogen, protein C, and protein Z. A significant c(2) effect was found for cholesterol, and plasma levels of FII, FV, vWF, antithrombin, protein S, plasminogen, and TFPI, ranging from 9.3% to 33.2%. CONCLUSIONS: Our research stresses the importance of research on the genetic variability and lifestyle modifications of risk factors associated with pediatric stroke.