Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.
Testosterone is an important hormone in the sexual differentiation of the brain, contributing to differences in cognitive abilities between males and females. For instance, studies in clinical populations such as females with congenital adrenal hyperplasia (CAH) who are exposed to high levels of androgens in utero support arguments for prenatal testosterone effects on characteristics such as visuospatial cognition and behaviour. The comparison of opposite-sex (OS) and same-sex (SS) twin pairs can be used to help establish the role of prenatal testosterone. However, although some twin studies confirm a masculinizing effect of a male co-twin regarding for instance perception and cognition it remains unclear whether intra-uterine hormone transfer exists in humans. Our aim was to test the potential influences of testosterone on academic performance in OS twins. We compared ninth-grade test scores and teacher ratings of OS (n=1812) and SS (n=4054) twins as well as of twins and singletons (n=13,900) in mathematics, physics/chemistry, Danish, and English. We found that males had significantly higher test scores in mathematics than females (.06-.15 SD), whereas females performed better in Danish (.33-.49 SD), English (.20 SD), and neatness (.45-.64 SD). However, we did not find that OS females performed better in mathematics than SS and singleton females, nor did they perform worse either in Danish or English. Scores for OS and SS males were similar in all topics. In conclusion, this study did not provide evidence for a masculinization of female twins with male co-twins with regard to academic performance in adolescence.
Cites: Behav Genet. 1993 Jul;23(4):323-98240211
Cites: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11900-48265645
We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson's disease have not been validated against clinical information.
Parkinson's disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998-2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study).
Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years.
Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence.
Cites: Arch Neurol. 1999 Jan;56(1):33-99923759
Cites: Clin Auton Res. 1998 Dec;8(6):359-629869555
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 20, Helsinki, FI-00014, Finland; Finnish Gymnastics Federation, Hämeentie 105 A, 00550 Helsinki, Finland. Electronic address: email@example.com.
Obes Res Clin Pract. 2019 Nov - Dec; 13(6):522-528
To determine the accuracy of self-reported height, weight, body mass index (BMI) and waist circumference (WC) compared to the measured values, and to assess the similarity between self-reported and measured values within dizygotic (DZ) and monozygotic (MZ) twin pairs.
The data on self-reported and measured height, weight and WC values as well as measured hip circumference (HC) were collected from 444 twin individuals (53-67 years old, 60% women). Accuracies between self-reported and measured values were assessed by Pearson's correlation coefficients, Cohen's kappa coefficients and Bland-Altman 95% limits of agreement. Intra-class correlation was used in within-pair analyses.
The correlations between self-reported and measured values were high for all variables (r=0.86-0.98), although the agreement assessed by Bland-Altman 95% limits had relatively wide variation. The degree of overestimating height was similar in both sexes, whereas women tended to underestimate and men overestimate their weight. Cohen's kappa coefficients between self-reported and measured BMI categories were high: 0.71 in men and 0.70 in women. Further, the mean self-reported WC was less than the mean measured WC (difference in men 2.5cm and women 2.6cm). The within-pair correlations indicated a tendency of MZ co-twins to report anthropometric measures more similarly than DZ co-twins.
Self-reported anthropometric measures are reasonably accurate indicators for obesity in large cohort studies. However, the possibility of more similar reporting among MZ pairs should be taken into account in twin studies exploring the heritability of different phenotypes.
Questionnaire surveys provide an efficient means of identifying potential seizure cases in large population-based cohorts. Concerns exist, however, with regard to the reliability of self-reported information both with respect to the validity of the results obtained and with regard to the usefulness of this approach in identifying true cases. Information on history of seizures obtained by questionnaire from members of 47,626 twin pairs included in the Mid-Atlantic (MATR), Danish (DTR) and Norwegian (NTR) Twin Registries was verified using medical records and detailed clinical and family interviews. The accuracy of these reports was assessed. Self-reported epilepsy was verified in 81.9% of twins overall (86.1% (DTR), 75.6% (NTR) and 80.7% (MATR)). However, when both pair members reported a history of epilepsy in the affected pair member, epilepsy was verified in >90% of cases. Among MATR twins with a verified history of epilepsy, 21.5% reported other seizures but not epilepsy and 18.5% of verified Norwegian epilepsy cases reported no history of epilepsy themselves and were identified only through their co-twin. The results of this study indicate that the accuracy of self-reported epilepsy and febrile seizures among those who provided information on health history was high across all populations. However, the relatively large percentage of twins with a verified diagnosis who did not acknowledge epilepsy suggests that the frequency of epilepsy may be under-estimated in self-reported samples.
The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI-discordant monozygotic (MZ) twin pairs were studied.
Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel-electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI-discordant (within-pair difference [?] in BMI >3 kg/m2) and nin concordant (?BMI
Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.
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