Heritability of cilioretinal arteries: a twin study

PURPOSE: To determine whether the presence of one or more cilioretinal arteries, a distinct element of the pattern of fundus vessels, is genetically programmed, influenced by environmental factors, or the result of random mechanisms of vascular development. METHODS: The fundi of 112 pairs of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. RESULTS: Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes. The majority of cilioretinal arteries, 88.2%, were located temporally, and 11.8% were located nasally. Monozygotic twins had higher concordance rates for cilioretinal arteries than dizygotic twins. Tetrachoric correlations and Mantel-Haenszel odds ratios demonstrated statistically significant evidence of a genetic effect underlying the presence of cilioretinal arteries (P < 0.01). Statistical analysis supported the hypothesis that additive genetic factors influenced the presence of cilioretinal arteries with a heritability of 71.4%, the remaining variance being attributable to nonshared or random environmental factors. CONCLUSIONS: The presence or absence of one or more cilioretinal arteries in healthy persons is markedly influenced by genetic factors.     

Regular use of non‐steroidal anti‐inflammatory drugs increases the risk of adult‐onset asthma: a population‐based follow‐up study

Background: Little is known about the relation between regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult‐onset asthma. Methods: Using data from two multidisciplinary postal questionnaire surveys concerning health and lifestyle, we prospectively studied 19 349 adult twins enrolled in the nationwide Danish Twin Registry. Results: We found a higher prevalence of new‐onset asthma in subjects who used NSAIDs (other than aspirin) regularly compared with non‐users (7.7% vs 4.3%), OR = 1.87 (1.25–2.81), P = 0.002. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema and intake of medications other than NSAIDs, OR = 1.90 (1.26–2.85), P = 0.002. Conclusions: Regular use of NSAIDs other than aspirin may be a risk factor for adult‐onset asthma. This observation must be accommodated in explanations of the relationship between use of analgesics and risk of asthma. Please cite this paper as: Thomsen SF, Kyvik KO, Skadhauge LR, Steffensen I and Backer V. Regular use of non‐steroidal anti‐inflammatory drugs increases the risk of adult‐onset asthma: a population‐based follow‐up study. The Clinical Respiratory Journal 2009; 3: 82–84.     

Concordance of Inflammatory Bowel Disease among Danish Twins: Results of a Nationwide Study

Background: Previous studies have shown an increased risk of inflammatory bowel disease (IBD) among relatives of patients with Crohn disease and ulcerative colitis. In the present study the probandwise concordance rates for ulcerative colitis and Crohn disease among mono- and dizygotic twins were estimated. Further we aimed to evaluate whether smoking habits might influence the concordance, and to look for clinical characteristics of concordant versus discordant twin pairs. Methods: Among the 38,507 identified twins born in Denmark from 1953 to 1982, a questionnaire was sent to the 34,076 who previously had accepted to participate in studies. For twins reporting IBD, the diagnosis was verified by applying standard criteria to records requested from hospitals or practitioners. Results: Among the 29,421 (86.3%) twins answering the questionnaire, 103 pairs had at least one twin who suffered from IBD. In the Crohn disease group five of 10 monozygotic pairs, but none of 27 dizygotic pairs were concordant. In the ulcerative colitis group three of 21 monozygotic, and two of 44 dizygotic pairs were concordant. The probandwise concordance rate among monozygotic pairs was 58.3% for Crohn disease and 18.2% for ulcerative colitis; among the dizygotic pairs the rates were 0 and 4.5%, respectively. The frequency of smokers was higher among twins with Crohn disease and lower among twins with ulcerative colitis compared to the frequency in the twin register. Furthermore, smoking habits were found to be of significance for discordance for disease. Regarding the clinical characteristics no homogenous pattern was observed within the concordant pairs and the differences between concordant and discordant pairs were not significant. Conclusion: The observation of a significantly higher concordance rate among monozygotic than among dizygotic twin pairs strongly points to a genetic influence on occurrence of IBD, which seems to be more pronounced with regard to Crohn disease than to ulcerative colitis. Differences in smoking habits among the members of the discordant twin pairs may influence the discordance.     

Genetic architecture of circulating lipid levels

Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.     

Clinical characteristics and consequences of hand eczema - an 8-year follow-up study of a population-based twin cohort

Background:  Few population-based clinical follow-up studies on hand eczema are reported.
Objectives:  The aim of this study was to characterize clinical symptoms and to examine occupational and medical consequences as well as persistence of hand eczema in a population-based twin cohort.
Patients/Methods:  A total of 274 individuals with and without hand eczema were examined, patch tested, and interviewed in 1997–1998 and 2005–2006. Data on 188 individuals with hand eczema in 2005–2006 were analysed.
Results:  Erythema and scaling were the most frequent symptoms, and fingers and palms were most often affected. Mean hand eczema severity index score in individuals with clinical symptoms was 12.0. Sick leave was reported by 12.4%; job change by 8.5%. Being in the lowest socio-economic group and atopic dermatitis were risk factors for sick leave [odds ratio (OR) = 5.6; 95% confidence interval (95% CI) 1.5–22.9 and OR = 2.9; 95% CI 1.0–8.1]. The majority (63.4%) had seen a doctor at least once, and atopic dermatitis was a risk factor for more than 1 visit (OR = 3.0; 95% CI 1.4–6.4). Duration of >10 years was a risk factor for persistence of symptoms, which was reported by 67.7%.
Conclusions:  The clinical picture and consequences of hand eczema vary; however, the majority experience chronic symptoms.