An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.
To investigate whether sex-specific associations exist between migraine, lifestyle or socioeconomic factors. We distinguished between the subtypes migraine with aura (MA) and migraine without aura (MO). In 2002, a questionnaire containing validated questions to diagnose migraine and questions on lifestyle and socioeconomic factors was sent to 46,418 twin individuals residing in Denmark. 31,865 twin individuals aged 20-71 were included. The twins are representative of the Danish population with regard to migraine and other somatic diseases and were used as such in the present study. An increased risk of migraine was significantly associated with lower level of schooling and education, retirement, unemployment, and smoking. A decreased risk of migraine was significantly associated with heavy physical exercise and intake of alcohol. Direct comparison between the subtypes showed a decreased risk of MA compared to MO in subjects with low education or weekly intake of alcohol. The risk of MA was increased compared to MO in unemployed or retired subjects. Direct comparison between sexes showed a decreased risk of migraine for men compared to women in subjects who were low educated, unemployed or studying. The risk was increased for men compared to women in subjects with heavy physical exercise, intake of alcohol, and body mass index >25. Migraine was associated with several lifestyle and socioeconomic factors. Most associations such as low education and employment status were probably due to the negative effects of having migraine while others such as smoking were risk factors for migraine.
Cites: Cephalalgia. 2003 Jun;23(5):336-4312780762
Cites: Twin Res. 2002 Oct;5(5):352-712537858
Cites: Twin Res. 2003 Oct;6(5):422-3114624726
Cites: Neurology. 2005 Feb 22;64(4):600-715728279
Cites: Neurology. 2006 Feb 28;66(4):545-5016354886
We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations.
Do birthweight (BW) and co-twin sex influence the age at menarche in twins?
BW, but not co-twin sex, was associated with age at menarche in twins. However, BW was not associated with age at menarche after controlling for genetics and shared rearing environment.
Nutritional deprivation during critical developmental periods can trigger long-term effects on health. A small size at birth has been associated with early age at menarche in singletons. However, the relative influence of genetics and environmental factors on this association remains unresolved.
In total, 2505 twin pairs were included in this cohort study.
All participants were recruited from the Danish Twin Register. Data on the age at menarche were collected by questionnaire and combined with data on BW, birth length (BL) and gestational age (GA) from the Danish Medical Birth register. The BW for GA standard deviation score (BW-SDS) was calculated.
BW-SDS [hazard ratio (HR) 0.96; 95% confidence interval (CI): 0.93-0.00], P = 0.04], but not BW, BL or GA (P = 0.15), was positively associated with age at menarche in all twins after adjustment for zygosity and year of birth. However, BW-SDS was not associated with menarcheal age within twin pairs (HR 1.01; 95% CI: 0.91-1.12, P = 0.88). No differences were found in the age at menarche or birth size between twin girls from same sex and twin girls from opposite-sex pregnancies. Heritability of menarcheal age and BW were estimated to be 0.61 (95% CI: 0.38-0.84) and 0.27 (95% CI: 0.18-0.38), respectively. Both BW and menarcheal age were influenced by genetic and environmental factors.
A limitation of this study is recall bias on the age at menarche. It is also not clear how these results should be extrapolated to the non-twin population.
lower BW for GA is associated with earlier age at menarche in twin girls. However, the lack of within-pair differences in menarcheal age between even markedly BW-discordant twins indicates that this association is governed by environmental or genetic factors shared by both twins. Thus, within-pair differences in intrauterine nutritional factors leading to discordant growth do not seem to influence timing of menarche.
The authors have nothing to declare. Departmental funds were used to support all authors during the study period and preparation.
Epidemiological cancer data shed light on key questions within basic science, clinical medicine and public health. For decades, Denmark has had linkable health registers that contain individual level data on the entire population with virtually complete follow-up. This has enabled high quality studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses. However, methodological challenges still remain to be addressed, especially in cancer epidemiology studies among the elderly and the oldest-old. For example, a characteristic pattern for many cancer types is that the incidence increases up to a maximum at about ages 75-90 years and is then followed by a decline or a leveling off at the oldest ages. It has been suggested that the oldest individuals may be asymptomatic, or even insusceptible to cancer. An alternative interpretation is that this pattern is an artifact due to lower diagnostic intensity among the elderly and oldest-old caused by higher levels of co-morbidities in this age group. Currently, the available cancer epidemiology data are not able to provide clear evidence for any of these hypotheses.
Animal models and a few human studies have suggested a complex interaction between cancer risk and longevity indicating a trade-off where low cancer risk is associated with accelerating aging phenotypes and, vice versa, that longevity potential comes with the cost of increased cancer risk. This hypothesis predicts that longevity in one twin is associated with increased cancer risk in the cotwin.
A total of 4,354 twin pairs born 1900-1918 in Denmark were followed for mortality in the Danish Civil Registration System through 2008 and for cancer incidence in the period 1943-2008 through the Danish Cancer Registry.
The 8,139 twins who provided risk time for cancer occurrence entered the study between ages 24 and 43 (mean 33 years), and each participant was followed up to death, emigration, or at least 90 years of age. The total follow-up time was 353,410 person-years and, 2,524 cancers were diagnosed. A negative association between age at death of a twin and cancer incidence in the cotwin was found in the overall analyses as well as in the subanalysis stratified on sex, zygosity, and random selection of one twin from each twin pair.
This study did not find evidence of a cancer-longevity trade-off in humans. On the contrary, it suggested that longevity in one twin is associated with lower cancer incidence in the cotwin, indicating familial factors associated with both low cancer occurrence and longevity.
Cites: Aging Cell. 2008 Jun;7(3):281-418331618
Cites: Sci Transl Med. 2011 Feb 16;3(70):70ra1321325617
To describe temporal trends in the incidence rate of surgically treated middle ear cholesteatoma in Danish children from 1977 to 2010.
Data on surgically treated middle ear cholesteatoma was drawn from the Danish National Patient Register. A change in incidence rate over time was examined using Poisson regression analysis, while the cumulative incidence proportion was estimated using life-tables.
A total of 5850 cases of surgically treated middle ear cholesteatoma distributed among 3874 children aged 0-15 years were identified. From 1977 to 2002 the age-standardized incidence rates for first-time surgically treated middle ear cholesteatoma increased from 8 to 15 per 100,000 person-years with an estimated annual increase of 1.8% (95% confidence interval (CI) 1.3-2.2%). From 2002 to 2010 the rates decreased from 15 to 10 per 100,000 person-years with an annual decrease of 5.4% (95% CI 3.2-7.5%). Age-specific incidence rates were at maximum around the age of 9 years during the whole period. The estimated cumulative incidence proportion at age 16 years based on the 2010 age-specific incidence rates was 0.16% (95% CI 0.09-0.32%) compared with 0.20% (95% CI 0.11-0.37%) based on the 2000 age-specific incidence rates.
From 2002 to 2010 there was a decrease in the incidence rate of first-time surgically treated middle ear cholesteatoma. The decrease was preceded by a significant increase in the incidence rate of middle ear ventilation tube insertion. However, further studies are needed to find possible explanations for the decrease.
To estimate the risk of surgically treated middle ear cholesteatoma in individuals with a nonsyndromic orofacial cleft and in their siblings compared with the general population.
Historical cohort study.
Using the unique civil registration number for linkage, data from three national registers were used for the Danish 1936-2009 birth cohorts. Hazard ratios (HRs) were estimated with Cox regression analyses using age as the underlying time variable. Individuals were followed from January 1, 1977 until time of surgically treated cholesteatoma, and censored at emigration, death, or end of follow-up (December 31, 2010).
A total of 8,593 individuals with nonsyndromic orofacial cleft and 6,989 siblings were identified, undergoing 201 and 21 first-time cholesteatoma surgeries, respectively. A 5% random sample of the Danish population comprising 249,708 persons without an orofacial cleft was created, and 175,724 siblings to these persons were identified. These controls underwent 485 and 332 first-time cholesteatoma surgeries, respectively. For individuals with cleft lip and palate the HR for cholesteatoma surgery was 14 (95% confidence interval [CI], 12-18) and for individuals with cleft palate the HR was 20 (95% CI, 16-24) when compared with the random sample. In siblings of individuals with cleft palate, the HR for cholesteatoma surgery was 2.1 (95% CI, 1.1-4.1) when compared with siblings of the random sample.
A 20-fold increase in the risk of cholesteatoma was found in individuals with cleft palate, whereas cleft lip did not pose a risk of cholesteatoma. Furthermore, the study indicates an increased risk of cholesteatoma in unaffected siblings of individuals with cleft palate.
OBJECTIVE: We sought to evaluate rates of hospitalizations for neurodegenerative disorders in a cohort of Danish metal manufacturing employees. METHODS: A retrospective cohort study was conducted from 1977 to 2002 among 27,839 male Danish metal-manufacturing employees, with 9,817 of those employed in departments engaged in mild or stainless-steel welding and 6,163 welders. RESULTS: The standardized hospitalization ratio and 95% confidence intervals (CI) for Parkinson's disease were 0.9 (CI = 0.7-1.2) for men in steel-manufacturing companies, 1.0 (CI = 0.7-1.5) for men in welding departments, and 0.9 (CI = 0.4-1.5) for welders. Observed numbers for other neurological conditions were small and not above population expectations. Analyses for time period worked, age, and duration of welding were unremarkable. CONCLUSIONS: This relatively large cohort study with long-term follow-up provides no support for the hypothesis that rates of hospitalization for Parkinson's disease or other neurological conditions are elevated under the exposure circumstances of these Danish workers.
Research Centre for the prevention of Infant Mortality and Congenital Illnesses, Institute of Public Health, University of Southern Denmark, JB Winsløws Vej 9, DK-5000 Odense, Denmark. email@example.com
OBJECTIVES: To determine if the anatomical severity of oral clefting affects familial recurrence in a large population based sample. To provide reliable recurrence risk estimates for oral cleft for first, second, and third degree relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229 relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for first, second, and third degree relatives and stratification by severity, specificity, parent of origin effect, and family size for first degree relatives. RESULTS: For cleft lip and palate probands we observed recurrence risks for first, second, and third degree relatives of respectively 3.5% (95% CI 3.1% to 4.0%), 0.8% (95% CI 0.6% to 1.0%), and 0.6% (95% CI 0.4% to 0.8%). Individuals affected by the most severe oral cleft had a significantly higher recurrence risk among both offspring and siblings, eg, the recurrence risk for siblings of a proband with isolated bilateral cleft lip with cleft palate was 4.6% (95% CI 3.2 to 6.1) versus 2.5% (95% CI 1.8 to 3.2) for a proband born with a unilateral defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in first degree relatives and the type of cleft is predictive of the recurrence type. Highly reliable estimates of recurrence have been provided for first cousins in addition to more accurate estimates for first and second degree relatives. These results and the majority of prior data continue to support a multifactorial threshold model of inheritance.