The Fertility Pattern of Twins and the General Population Compared: Evidence from Danish Cohorts 1945-64

Twin studies provide an important possibility for demographers to analyze patterns of heritability and to estimate structural models with controls for endowments. These possibilities are increasingly used in the context of fertility and related behaviors. A close congruence between the fertility patterns of twins and that of the general population, however, is an essential pre-condition in order to generalize the results of twin-based investigations of fertility and related behaviors to the general population. In this paper we therefore compare the fertility of Danish twins born 1945--64 to the fertility pattern of the general population born during the same period. Our analyses find a very close correspondence between the fertility pattern of twins and of the general population. There exist only few statistically significant differences, and the primary difference pertains to the fact that female twins have a slightly later onset of childbearing than non-twins. There are virtually no relevant differences between the fertility patterns of dizygotic and monozygotic twins.cohort fertility, Denmark, fertility, twin studies

Comparison of academic performance of twins and singletons in adolescence : follow-up study

Objectives To determine whether twins in recent cohorts show similar academic performance in adolescence to singletons and to test the effect of birth weight on academic performance in twins and singletons. Design Follow-up study. Setting Denmark. Participants All twins (n = 3411) and a 5% random sample of singletons (n = 7796) born in Denmark during 1986-8. Main outcome measures Test scores in ninth grade (age 15 or 16), birth weight, gestational age at birth, parents’ age, and parents’ education. Results Ninth grade test scores were normally distributed, with almost identical mean and standard deviations for twins and singletons (8.02 v 8.02 and 1.05 v 1.06) despite the twins weighing on average 908 g (95% confidence interval 886 to 930 g) less than the singletons at birth. Controlling for birth weight, gestational age at birth, age at test, and parents’ age and education confirmed the similarity of test scores for twins and singletons (difference 0.04, 95% confidence interval − 0.03 to 0.10). A significant, positive association between test score and birth weight was observed in both twins and singletons, but the size of the effect was small: 0.06-0.12 standard deviations for every kilogram increase in birth weight. Conclusions Although older cohorts of twins have been found to have lower mean IQ scores than singletons, twins in recent Danish cohorts show similar academic performance in adolescence to that of singletons. Birth weight has a minimal effect on academic performance in recent cohorts; for twins this effect is best judged relative to what is a normal birth weight for twins and not for singletons

The age at first birth and completed fertility reconsidered: findings from a sample of identical twins

In this paper we use new methods and data to reassess the relationship between the age at first birth and completed fertility. In particular we attempt to properly estimate the postponement effect, i.e., the reduction in fertility associated with a delay in childbearing, using a sample of Danish monozygotic twins born 1945--60 to control for unobserved heterogeneity. Within-MZ twin pair estimates of the postponement effect indicate that a one year delay in the first birth reduces completed fertility by about 3% for both males and females. The effect is significantly stronger for older cohorts, and it is stronger for females with a late desired entry into parenthood. Analyses that fail to control for unobservables underestimate this postponement effect between 10--25%, and they underestimate the annual decline of this effect by up to 50%. Moreover, our estimates indicate important changes across cohorts in the relevance of child-preferences and ability characteristics for the age at first birth and the pace and level of subsequent fertility. (AUTHORS)

Genetic analysis of cause of death in a bivariate lifetime model with dependent competing risks

A mixture model in multivariate survival analysis is presented, whereby heterogeneity among subjects creates divergent paths for the individual's risk of experiencing an event (i.e., disease), as well as for the associated length of survival. Dependence among competing risks is included and rendered testable. This method is an extension of the bivariate correlated gamma-frailty model. It is applied to a data set on Danish twins, for whom cause-specific mortality is known. The use of multivariate data solves the identifiability problem which is inherent in the competing risk model of univariate lifetimes. We analyse the in uence of genetic and environmental factors on frailty. Using a sample of 1470 monozygotic (MZ) and 2730 dizygotic (DZ) female twin pairs, we apply five genetic models to the associated mortality data, focusing particularly on death from coronary heart disease (CHD). Using the best fitting model, the inheritance risk of death from CHD was 0.39 (standard error 0.13). The results from this model are compared with the results from earlier analysis that used the restricted model, where the independence of competing risks was assumed. Comparing both cases, it turns out, that heritability of frailty on mortality due to CHD change substantially. Despite the inclusion of dependence, analysis confirms the significant genetic component to an individual's risk of mortality from CHD. Whether dependence or independence is assumed, the best model for analysis with regard to CHD mortality risks is an AE model, implying that additive factors are responsible for heritability in susceptibility to CHD. The paper ends with a discussion of limitations and possible further extensions to the model presented.

The Danish political twin study:Political traits in Danish twins and the general population

We compare a recent Danish twin survey on political attitudes and behaviors to a nationally representative survey covering similar topics. We find very similar means and variances for most of our constructed scales of political attitudes and behaviors in the two surveys, although even small differences tend to be statistically significant due to sample size. This suggests that the twin study can be used to make inferences on the heritability of several political traits in the Danish population.</jats:p

The influence of smoking and BMI on heritability in susceptibility to coronary heart disease

Cause-specific mortality data on Danish monozygotic (MZ) and dizygotic (DZ) twins are used to analyze the influence of smoking and body mass index (BMI) on heritability estimates of susceptibility to coronary heart disease (CHD). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive and answered a questionnaire, including information about smoking, height and weight, in 1966. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from 1 January 1966 to 31 December 1993. We use the correlated gamma-frailty model with observed covariates for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.54 (0.16) after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD. No evidence for common genetic factors acting on smoking, BMI, and susceptibility to CHD are found which indicates that the association between smoking and susceptibility to CHD and BMI and susceptibility to CHD is not confounded by common genetic factors.

On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins

Udgivelsesdato: 2008-Jan-24OBJECTIVE: In a nationwide unselected twin population to estimate the relative importance of genetic and environmental effectors in the etiopathogenesis of psoriatic arthritis (PsA). METHODS: The study comprised three Danish nationwide twin cohorts. In 1994 and 2002 a total of 37,388 and 46,418 Danish twin individuals respectively were asked by questionnaire if they had PsA. Twins reporting PsA were invited to participate in a clinical examination. Patients were classified according to the Moll and Wright (M&amp;W) and the CASPAR criteria. Heritability was estimated by probandwise concordance rates and variance component analysis. RESULTS: 228 twin individuals reported PsA. Following diagnostic validation in 184 (81%), 50 probands were diagnosed with PsA according to the M&amp;W criteria. Five of their co-twins were either dead, had emigrated, or did not participate in the twin study and nine did not respond, resulting in 36 complete pairs. A total of 1/10 MZ pairs and 1/26 DZ pairs were concordant for PsA, yielding a 6.2% difference in proportions (95% CI: -11%, 37%). 5/10 MZ pairs and 4/26 DZ pairs were concordant for psoriatic skin disease implying a 35% difference (95% CI: 2%, 60%, p &lt; 0.05). CONCLUSION: This first twin study on PsA confirms that genes are important in the causation of psoriatic skin disease. Despite the limited statistical power, the almost identical concordance rates for PsA in MZ and DZ twins stresses the importance of continued search for non genetic effectors in PsA

Heritability in political interest and efficacy across cultures:Denmark and the United States

Interest in politics is important for a host of political behaviors and beliefs. Yet little is known about where political interest comes from. Most studies exploring the source of political interest focus on parental influences, economic status, and opportunity. Here, we investigate an alternative source: genetic transmission. Using two twin samples, one drawn from Denmark and the other from USA, we find that there is a high degree of heritability in political interest. Furthermore, we show that interest in politics and political efficacy share the same underlying, latent genetic factor. These findings add to the growing body of literature that documents political behaviors and attitudes as not simply the result of socialization, but also as part of an individual's genetically informed disposition.</jats:p

Familial aggregation of atrial fibrillation: a study in Danish twins

BACKGROUND: Heritability may play a role in non-familial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared to a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) where one or both members were diagnosed with AF were identified in The Danish Twin Registry. Concordance rates were twice as high for MZ pairs than for DZ pairs regardless of gender, 22.0% vs. 11.6% (p<0.0001). In a Cox regression of event free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included, when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event free survival time (hazard ratio: 2.0 (95% confidence interval (CI): 1.3 – 3.0)) thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62 % (55 % – 68 %), due to additive genetics. There were no significant differences across genders. CONCLUSION: All the analyses of twin similarities in the present study indicate that genetic factors play a substantial role in the risk of AF for both genders. The recurrence risk for co-twins (12–22%) is clinically relevant and suggests that co-twins of AF-affected twins belong to a high-risk group for AF

Haptoglobin and CD163 in Aspects of Disease

I blodkredsløbet binder haptoglobin (Hp) hurtigt ekstracellulært hæmoglobin (Hb) for at forhindre oxidativ stress og vævsskade. Dette stærke kompleks genkendes og optages af den makrofagspecifikke receptor CD163, hvorefter det nedbrydes, hvilket gør, at jern kan genbruges. Formålet med denne afhandling er at undersøge proteinerne i dette Hb scavenger-system i forhold til forskellige aspekter af sygdomsudvikling og deres anvendelighed i diagnosticering af intravaskulær hæmolyse og ikke-alkoholisk fedtleversygdom (NAFLD).Ved betydelig hæmolyse kan Hp ikke måles i en blodprøve, da Hp-Hb komplekserne nedbrydes og opbruger derved kroppens Hb fangende kapacitet. Lave Hp plasma niveauer bruges derfor som en markør for hæmolyse i klinikken. Den analytiske metode der benyttes, afhænger af epitop genkendelse og er derfor følsom overfor tilstedeværelse af Hp-relateret protein (Hpr) og strukturelle forskelle mellem Hp fænotyperne. Derfor blev specifikke målemetoder udviklet der kan differentiere mellem Hp og Hpr og fænotype-specifikke standard benyttes for at overkomme udfordringerne med oligomerisering af Hp. Dette viste, at brug af en uparret standard medførte en signifikant bias især i patienter med Hp1-1 fænotype (Paper I) og, at tilstedeværelsen af Hpr var underordnet og påvirkede ikke målingerne signifikant. Derudover korrelerede koncentrationen af Hpr signifikant med Hp fænotype og plasmakoncentration. Hpr faldt også under hæmolyse, samtidig med at Hp faldt (Paper II). Endelig blev en forklaring på hvorfor man generelt ser en lavere Hp koncentration hos person med Hp1-1 fænotyper ift personer med Hp2-1 eller Hp2-2 præsenteret.En opløselig form af CD163 (sCD163) frigives til cirkulationen i forbindelse med makrofag aktivering. Øget plasmakoncentration af sCD163 er associeret til en række inflammatoriske sygdomme blandt andet ikke-alkoholisk steatohepatitis (NASH), som er den progressive form af NAFLD. I en kohorte af overvægtige patienter bekræftede øget plasmakoncentration af sCD163 blev sCD163 som en mulig ny biomarkør for NASH. Derimod faldt udtrykket af CD163 i parrede lever biopsier i takt med sværere grad af NAFLD (Paper III). Denne negative association blev yderligere undersøgt i mus der blev fodret med en vestlig diæt. I takt med at mere fedt akkumulerede i leveren faldt det hepatiske udtryk af CD163. Derudover forværrede manglen af CD163 udviklingen af steatose i leveren i de tidlige stadier hvilket antyder en beskyttende effekt af CD163 i fedtdeponering. Dette indikerer samlet set at makrofager besidder en vigtig patologisk rolle i udviklingen af NAFLD, som potentiel kan udnyttes i behandling af sygdommen (Paper IV).Extracellular hemoglobin (Hb) is rapidly captured by haptoglobin (Hp) in the circulation to preventoxidative stress and tissue damage. This tight complex is recognized and endocytosed by themacrophage-specific scavenger receptor CD163 leading to lysosomal degradation of the Hp-Hbcomplex and reuse of the components maintaining iron homeostasis. The aim of this thesis is toexplore the proteins within this Hb scavenging system in relation to aspects of pathogenesis and theirutility in diagnosis of intravascular hemolysis and non-alcoholic fatty liver disease (NAFLD). During excessive hemolysis, Hp is virtually undetectable in plasma because the Hp-Hb complexes are degraded and the Hb scavenging capacity is exhausted. Thereby low Hp levels are used in the clinic as a biomarker of hemolysis. The clinical analytical methods rely on epitoperecognition which is challenged by the presence of Hp-related protein (Hpr) with the same epitopesand by complex structural differences between Hp phenotypes. Therefore, specific assays that differentiated between Hp and Hpr were generated, and phenotype-specific calibrators were used toovercome the oligomerization challenge. This uncovered a significant bias using unmatched calibrators especially in patients with the Hp1-1 phenotype (Paper I), but also revealed that thepresence of Hpr has negligible influence on the measurements. Furthermore, the data showed that the concentration of Hpr correlated significantly with Hp phenotype and plasma concentrations. In fact, Hpr was also reduced during hemolysis concurrently with Hp (Paper II). Finally, the data provided evidence for a model explaining why Hp1-1 individuals generally have a lower Hp concentration compared to Hp2-1 and Hp2-2 individuals.A soluble form of CD163 (sCD163) is released to the circulation during macrophage activation which has been associated with various inflammatory conditions such as non-alcoholic steatohepatitis (NASH), which is the progressive form of NAFLD. Increased plasma levels of sCD163 confirmed sCD163 as a potential biomarker of NASH in a unique cohort of obese patientsbefore bariatric surgery. Matched liver biopsies revealed a concurrent reduction in CD163 expression in more severe NAFLD (Paper III). This negative association was further investigated in western diet-fed mice. As steatosis intensified the expression of CD163 decreased in the liver and CD163 deficiency exacerbated hepatic steatosis in early stages of steatosis suggesting a protective role of CD163 in fat deposition in the liver. Overall, this indicates a pathological importance of macrophages in the development of NAFLD that potentially can be used in therapy (Paper IV)