The heritability of Dupuytren's disease: familial aggregation and its clinical significance

PURPOSE: Dupuytren's disease (DD) is a benign, fibroproliferative disease affecting the hands. The familial occurrence of DD and its presence in identical twins suggests a genetic basis for the condition. Our aims in this study were (1) to provide evidence for familial aggregation of DD by estimating the sibling recurrence-risk ratio and (2) to link previously associated environmental risk factors with family history of DD. METHODS: Patients diagnosed with DD between the ages of 58 and 81 years (N = 92) were interviewed to assess potential risks and the severity of their conditions. A clinical history and examination were performed and we attempted to interview every family member either in person or through a postal questionnaire. RESULTS: The sibling recurrence-risk ratio (lambda(s)) equaled 2.9 and ranged from 2.6 to 3.3 based on the 95% confidence intervals for the population prevalence. This suggests a high genetic basis for the causation of DD. A lower age of onset and greater severity of DD were associated significantly with a positive family history of DD. Other factors showed no statistical significance with familial aggregation of DD. CONCLUSIONS: The familial clustering observed in DD likely is due to genetic influence rather than shared environment, as shown by the lack of association with exposure to environmental risk factors and family history. Understanding the genetic basis of DD is important for developing novel diagnostic, preventative, and therapeutic regimens in the future. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic, Level II.     

A multivariate analysis of the genetics of fearfulness in potential guide dogs

Fearfulness is the most common reason causing dogs to be unsuitable for training as guide dogs. We have carried out a diallel cross using four breeds of dog—Labrador, German shepherd, boxer, and kelpie—and recorded 38 measures of fearfulness. The variation between litters was described by three discriminant functions. One function, which measured general fearfulness, showed significant genetic variation but no nongenetic between-litter variation. The other two functions showed a mixture of genetic and environmental variation. Of the three functions, only general fearfulness affected a dog's suitability as a guide dog. Labradors were the least fearful and German shepherd dogs the most fearful of the four breeds. There was no heterosis for general fearfulness, but there was significant within-breed genetic variation, implying that fearfulness could best be reduced by a selection program among Labradors. Optimum methods of selecting against general fearfulness are discussed.This work was supported by a grant from the Uncle Bens Company in Australia and overseas.     

Genetic Influence in Headaches: A Swedish Twin Study

The heritability of liability to self-reported migraine and nonmigrainous headaches was examined in two large cohorts from the Swedish Twin Registry consisting of 6448 (the older cohort) and 12 884 (the younger cohort) like-sexed twin pairs. Higher concordance rates were consistently found for lifetime migraine among the monozygotic twins than in the dizygotic twins, as well as for migraine headaches of the recurrent disabling type. In addition, a higher concordance rate was found among the monozygotic twins than in dizygotic twins in a "mixed" group of possible tension-type or mild migraine headaches (or both). The results of structural equation model-fitting analyses showed that genetic effects for migraine headaches were stronger for the females (estimates ranging from 49% to 58%) than for the males (39% to 44%) in the two cohorts. Unique nonshared environmental effects were greatest for the "mixed" group in both sexes (estimates ranging from 60% to 69%). The results are discussed in view of similar large-scale twin studies examining the heritability of liability to migraine.     

The genetics of quantifiable homeostasis: I. The general issues

Some fundamental issues in developing the quantitative genetics of heritable traits are addressed. Such a trait must be capable of being represented as a quantity. Choice of the metric can be satisfactorily made only in the light of some insight into the nature of the trait and what its revealing characteristics may be. This insight is likely to change as more is known about the process, so the form and detail of the analysis is not static but perhaps continually evolving. Much has been made out of sample means and, at a more sophisticated level, Galton-Fisher theory (the analysis of the first two moments of multivariate Gaussian variates). However, at least some processes seriously violate the assumptions underlying that theory. One such group comprises traits in which the means are unvarying and the genetic message lies in other aspects of the distribution; in these circumstances the standard summary statistics such as heritability, regression, and correlation may be totally uninformative, distracting, or even misleading. This paradox is illustrated by reference to homeostasis, where the Mendelian component lies, not in the mean, but in the degree of laxity of control. Since estimating higher moments is notoriously imprecise, the suggested remedy is the familiar and commonsense one of exploring the genetics of the intermediate states and underlying mechanisms and not only that of the resultant (“bottom-line”) phenotype. In our chosen problem, the task of relating the outcome to the basic mechanism of inheritance calls for a detailed understanding of the homeostasis involved.     

Minimal genetic influences on plasma fibrinogen level in adult males in the NHLBI twin study

Plasma fibrinogen was determined in 189 twins participating at the Indiana center during the third examination of the NHLBI twin study with a mean age of 63 years. Moderate heritability estimates were obtained from 44 complete MZ pairs and 39 complete DZ pairs. After adjustment of fibrinogen levels for age and other confounding variables related to cardiovascular disease risk, the maximum likelihood heritability estimate was only 30% (p = 0.03). Plasma fibrinogen was most strongly associated with smoking and the presence of diabetes. Omitting all subjects with diabetes or cardiovascular disease further reduced the heritability estimates slightly, and most path models including genetic parameters provided no significant improvement in fit over a model determined solely by random environmental effects. Our results are consistent with the environment rather than genetic influences having a greater influence on the level of plasma fibrinogen.     

Genes and cigarette smoking

AIMS: Attempts to further our understanding of the determinants of cigarette smoking, tobacco addiction and related behaviours have included the dissection of genetic influences on these phenotypes. This review summarizes the current state of evidence from both twin and adoption studies and molecular genetic studies. We also review future research horizons and the direction which studies of this kind are likely to take in the near future. FINDINGS: There is consistent evidence from twin and adoption studies that genetic factors play a role in the aetiology of cigarette smoking. Nevertheless, despite a large number of candidate gene studies, and a smaller number of linkage studies, few reported associations and chromosomal regions of interest have proved to replicate reliably. This is due most probably to the small effects of individual loci on complex behaviours such as smoking. CONCLUSIONS: Future research is likely to include the study of gene x environment interactions (including gene x treatment interactions, which offer the prospect of genetically tailored smoking cessation treatment) and the use of more sophisticated smoking-related phenotypes, such as longitudinal smoking trajectories, and intermediate phenotypes which use technologies such as neuroimaging and other laboratory and biobehavioural measures.     

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。