Pia Svedberg

The Swedish Twin Registry in the third millennium.

Since the Swedish Twin Registry was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases, it has been expanded and updated on several occasions. The focus has similarly broadened to most common complex diseases. The content of the database is described, ongoing projects based on the registry are summarized, and we review some of the principal findings on aging, cancer and cardiovascular disease that have come from the registry. Ongoing efforts and future plans for the STR are discussed. Among others, we plan blood collection and genotyping to study the genetic bases of complex diseases, a first contact ever with the cohorts born after 1958, and in-depth studies of selected diseases, such as Parkinsons disease and chronic fatigue syndrome.

Genetic Liability to Disability Pension in Women and Men: A Prospective Population-Based Twin Study

Background Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all. Methods The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling. Results During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes. Conclusions The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men.

Are self-report of disability pension and long-term sickness absence accurate? Comparisons of self-reported interview data with national register data in a Swedish twin cohort

BackgroundSelf-reported disability pension (DP) and sickness absence are commonly used in epidemiological and other studies as a measure of exposure or even as an outcome. The aims were (1) to compare such self-reports with national register information in order to evaluate the validity of self-reported DP and sickness absence, and (2) to estimate the concordance of reporting behaviour in different twin zygosity groups, also by sex.MethodsAll Swedish twins born 1933-1958 who participated in the Screening Across the Lifespan Twin study (SALT) 1998-2003, were included (31,122 individuals). The self-reported DP and long-term sickness absence (LTSA) at the time of interview was compared to the corresponding register information retrieved from the National Social Insurance Agency by calculating the proportions of agreements, kappa, sensitivity, specificity, concordance rates, and chi-square test, to evaluate construct validity.ResultsThe proportions of overall agreement were 96% and specificity 99% for both DP and LTSA, while the sensitivity was 70% for DP and 45% for LTSA. Kappa estimates were 0.76 for DP, and 0.58 for LTSA. The proportions of positive agreement were 64% for DP and 42% for LTSA. No difference in response style was found between zygosity groups among complete twin pairs for DP and LTSA. Results were similar for women and men and across age. Kappa estimates for DP differed somewhat depending on years of education, 0.68 (college/university) vs. 0.77 (less than 13 years in school) but not for LTSA.ConclusionsSelf-reported DP data may be very useful in studies when register information is not available, however, register data is preferred especially for LTSA. The same degree of twin similarity was found for truthful self-report of DP and LTSA in both monozygotic and dizygotic twin pairs. Thus, the response style was not influenced by genetic factors. One consequence of this would be that when estimating the relative importance of genetic and environmental effects from twin models, heritability estimates would not be biased.

Night work and breast cancer in women: a Swedish cohort study

Objectives Recent research has suggested a moderate link between night work and breast cancer in women, mainly through case–control studies, but non-significant studies are also common and cohort studies are few. The purpose of the present study was to provide new information from cohort data through investigating the association between the number of years with night work and breast cancer among women. Design Cohort study of individuals exposed to night shift work in relation to incidence of breast cancer in women. Setting Individuals in the Swedish Twin registry, with follow-up in the Swedish Cancer Registry. Participants 13 656 women from the Swedish Twin Registry, with 3404 exposed to night work. Outcome measures Breast cancer from the Swedish Cancer Registry (463 cases) during a follow-up time of 12 years. Results A Cox proportional hazards regression analysis with control for a large number of confounders showed that the HR was HR=1.68 (95% CI 0.98 to 2.88) for the group with >20 years of night work. When the follow-up time was limited to ages below 60 years, those exposed >20 years showed a HR=1.77 (95% CI 1.03 to 3.04). Shorter exposure to night work showed no significant effects. Conclusions The present results, together with previous work, suggest that night work is associated with an increased risk of breast cancer in women, but only after relatively long-term exposure.

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins

BackgroundStability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account.MethodsThe study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008.ResultsDuring the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding.ConclusionsHealth behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons.

Health-related risk factors for disability pensions due to musculoskeletal diagnoses: A 30-year Finnish twin cohort study

Aims: There is a need to better understand work incapacity due to musculoskeletal disorders (MSD) and the factors that contribute to being granted disability pension (DP) with such disorders. A twin cohort study would serve a powerful tool responding to this knowledge gap by providing information on factors affecting DP when controlling for family background. The purpose was to investigate the incidence of and risk factors for DP due to any MSD (n = 1,819) and specifically due to osteoarthritis (OA, n = 677) in a twin cohort of 24,043 people over a 30-year follow-up. Methods: Data on twin pairs from a mailed questionnaire during the baseline year of 1975 were followed up with register data regarding DP, emigration, old-age pension, and death. For statistical analysis, univariate and multivariate Cox proportional hazard ratios were estimated. Results: Baseline musculoskeletal pain, frequency of use of analgesics, body mass index, and chronic diseases, as well as education and social class were significant risk factors for DP due to MSD at follow-up in both sexes. These factors were also the significant predictors of DP due to OA in men. In women, DP due to OA was best predicted by baseline musculoskeletal pain and lower social class. Conclusions: The risk of DP due to MSD and OA seemed to be influenced by comorbidities, educational level and social class. Analyses of twin pairs discordant for DP confirmed the results. Accumulated health problems and chronic conditions during the life course may lead to permanent work incapacity.

Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study.

Little is known about the role of genetic and environmental factors in irritable bowel syndrome. Various extra‐intestinal manifestations are more prevalent in cases than in controls. Genetic effects may be important in the liability to develop functional bowel disorders.

Health-Related and Sociodemographic Risk Factors for Disability Pension due to Low Back Disorders A 30-Year Prospective Finnish Twin Cohort Study

Objectives: To investigate health-related and sociodemographic risk factors for disability pensions (DP) due to low back disorders (LBD). Methods: Questionnaire data in 1975 of the Finnish Twin Cohort Study with record linkage to information on DP due to LBD from the official pension registers during follow-up 1975 to 2004 was analyzed with Cox proportional hazard models. Results: Musculoskeletal pain (Hazards Ratio [HR] = 2.36 to 2.39; 95% CI 1.97 to 2.88), smoking (HR = 1.82; 1.49 to 2.22), frequent analgesics use (HR = 1.67; 1.38 to 2.02), and presence of other chronic disease (HR = 1.44; 1.22 to 1.70) increased the risk for DP due to LBD. Years of education decreased the risk (HR = 0.81; 0.77 to 0.85). Associations remained significant when adjusted for familial background. Conclusions: Health-related and sociodemographic risk factors for DP due to LBD can be identified early in life, and they seem independent from familial effects.

Mortality among disability pensioners in Norway and Sweden 1990-96 : Comparative prospective cohort study

Aim: The aim of the study was to assess excess mortality related to disability pension (DP) status and DP diagnoses in Norway and Sweden during 1990—96. Methods: Representative samples of the population aged 30—59 years, without DP at baseline 1 January 1990, 71,293 women and 76,928 men from Norway, and 68,181 women and 71,950 men from Sweden, were followed up during 1990—96. Granting of DP, DP diagnosis, age and gender were explanatory variables in Cox proportional hazards analysis with death from all causes as the outcome variable. Results: Among women, 10.4% in Sweden and 7.1% in Norway obtained DP, as compared to 7.5% and 5.6% of the men. In Sweden, 66% of female and 49% of male DP recipients had musculoskeletal diagnoses, as compared to 40% and 27% in Norway. In Sweden, 3.0% of the women and 6.1% of the men with DP died, as compared to 4.6% and 8.5% in Norway. Hazard ratios (HRs) for women with DP vs. the non-DP group were 3.2 (95% confidence interval (CI)=2.7—3.8) in Sweden, and 4.9 (95% CI=4.1—5.7) in Norway. Among men with DP, there was no difference in mortality rate between the countries. HRs for men with musculoskeletal diagnoses vs. the non-DP group were 1.5 (95% CI= 1.1—2.0) in Norway and 1.4 (95% CI= 1.1—1.8) in Sweden. In both countries, the mortality rate among female disability pensioners with musculoskeletal diagnoses was not increased. Conclusions: The study confirmed an increased mortality rate among disability pensioners, except for women with musculoskeletal diagnoses. The mortality pattern related to DP diagnoses was similar in the two countries. A high frequency of musculoskeletal DP diagnoses among women with DP in Sweden explained a lower mortality rate as compared to Norway.

Heritability of endometriosis

OBJECTIVE To estimate the relative contribution of genetic influences and prevalence on endometriosis. DESIGN Analysis of self-reported data from a nationwide population-based twin registry. SETTING Not applicable. PATIENT(S) A total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Self-reported endometriosis, validated by medical records. RESULT(S) A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects. CONCLUSION(S) Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis.