BACKGROUND: The purpose of this study was to examine the association between total self-reported health-enhancing physical activity and country of birth among women living in Sweden. METHODS: Women (age 18 to 65 years) born in Sweden, Finland, Chile, and Iraq were recruited for this cross-sectional study. Data were collected by means of a postal questionnaire including the International Physical Activity Questionnaire (IPAQ-long version). Self-reported physical activity data were converted to MET-minutes per week and analyzed as continuous or categorical scores. A total of 2649 women were included in the analyses. The association between physical activity and country of birth was explored using ordinal logistic regression assuming proportional odds. RESULTS: The total physical activity differed significantly between the countries of birth (P
Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.
BACKGROUND: Few studies have investigated the possible differential transmission of maternal and/or paternal coronary heart disease (CHD) to offspring, after accounting for sociodemographic characteristics. METHODS: The Multigeneration Register was linked to hospital data in this study of all Swedish individuals born since 1932 and their parents. Registered cases of CHD between January 1, 1987, and December 31, 2001, were evaluated. Poisson regression was used to calculate standardized incidence ratios (SIRs) for men and women with mothers and/or fathers affected by CHD compared with men and women whose parents were not affected. All analyses were conducted in 2005. RESULTS: Maternal transmission was stronger than paternal transmission and the confidence intervals did not overlap. For women, the overall SIRs were 1.43 (95% confidence interval [CI]=1.34-1.51) for maternal transmission and 1.17 (95% CI=1.11-1.23) for paternal transmission. For men, the corresponding SIRs were 1.55 (95% CI=1.50-1.60) and 1.41 (95% CI=1.37-1.45). Even higher SIRs were found in the youngest age groups, among those with both parents affected by coronary heart disease, and among those with premature parental CHD. CONCLUSIONS: These findings might ultimately influence treatment decisions regarding risk factors and suggest the need for research focusing on genetic and intrauterine risk factors.
OBJECTIVE: In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses. METHODS: The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member. RESULTS: Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32). CONCLUSION: This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.
BACKGROUND AND PURPOSE: Previous studies of familial risks have often combined ischemic and hemorrhagic stroke even though it seems unlikely that these 2 very different pathological conditions are under the same genetic influence. This study is the first to investigate the concordant (same subtype) and disconcordant (different subtype) association between ischemic and hemorrhagic stroke. METHODS: Data of first hospitalization for stroke were obtained from the Hospital Discharge Register during the study period 1987 to 2001. All individuals born in Sweden from 1932 onwards were included and linked to their siblings. Risks were calculated as standardized incidence ratios and compared with individuals without affected siblings. Results were standardized for age, gender, geographical region and socioeconomic status. RESULTS: Ischemic stroke (n=25,630) was associated only with ischemic stroke (n=7961), which was also the case for hemorrhagic stroke. The statistically significant standardized incidence ratios were 2.14 (95% CI, 1.21 to 3.74) and 1.82 (95% CI, 1.21 to 2.75), respectively. For discordant subtypes of stroke no significant associations were found. CONCLUSIONS: The results suggest that ischemic and hemorrhagic stroke are not under the same genetic influence. However, further studies of the human genome are needed in order to identify the specific genes that play roles in the pathogenesis of common subtypes of stroke.
Population-level familial risks are not available for amyotrophic lateral sclerosis (ALS), and a few studies have analyzed familial association of ALS with other diseases. We used the Swedish Multigeneration Register to identify family members and link them to the Hospital Discharge Register to calculate standardized incidence ratios (SIRs) for familial association in ALS and 33 autoimmune diseases. Among 4,970 ALS patients, familial SIR for offspring of affected parents was 4.71, for singleton siblings, it was 29.83, and for members of multiplex families, it was 1,100; 1.1% of the offspring had an affected parent, and 2.2% an affected sibling. The high risks among siblings without affected parents may suggest recessive inheritance. The SIR for spouse correlation for ALS was 2.35 which may imply the influence of yet unknown environmental factors in ALS susceptibility. ALS associated with Behcet disease, multiple sclerosis, ulcerative colitis, and Wegener granulomatosis; however, chance associations cannot be excluded. In this first population level family study on ALS and 33 autoimmune and related conditions, we found high familial risks depending on the proband. These findings should guide future genomic studies. The high spouse correlation will be a challenge to environmental epidemiology of ALS.
Familial clustering of a disease is a direct indicator of a possible heritable cause, provided that environmental sharing can be excluded. If the familial clustering is lacking, the likelihood of a heritable influence is also small. In the era of genome scans, the consideration of data on heritability should be important in the assessment of the likely success of the genome scan. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. This Register has been extensively used to study a number of different diseases through linkage to the Hospital Discharge Register. In the present article we review the obtained and some unpublished results for nine main disease classes. For each of these, familial risks are given for four disease subtypes. As measures of familial clustering we use risks between siblings, twins and spouses. Disease correlation between spouses suggests environmental sharing and a higher correlation between siblings and particularly twins shows heritable effects. We will also comment on the established susceptibility genes and the risks conferred by them. The data suggest high heritabilities for chronic obstructive pulmonary disease, asthma, noninfective enteritis and colitis, cerebral palsy and endocrine and metabolic diseases. Among the performed first-generation genome scans on various diseases, the success appears to be related to the a priori heritability estimates. To our knowledge this is a first attempt to summarize familial risks for a large number of diseases using data from a single population on which reasonable uniform diagnostic criteria have been applied.
OBJECTIVE: Familial risks of depression have been assessed in small case-control studies, usually based on reported, but not medically verified depressions in family members; thus the degree of familial clustering for these diseases remains to be established. METHODS: We conducted a nationwide study on familial risks of depression linking the Multigeneration Register of 0-72-year-old individuals to the Hospital Discharge Register for diagnosed depression patients in Sweden from 1987 to 2004. Standardized incidence ratios (SIRs) were calculated for affected singleton siblings, twins, and spouses by comparing those whose siblings or spouses had no recorded hospitalization for depression. RESULTS: A total of 60 477 hospitalized cases and 3849 affected siblings were identified with a familial SIR of 2.95, which was independent of sex, age at diagnosis, and age differences between siblings. When both siblings were diagnosed with manic, bipolar, or major depression, the SIRs were 5.87, 10.23, and 2.79, respectively. The SIR for twin pairs was 4.57. The SIR for spouses was 1.76. CONCLUSION: The significantly higher risk for siblings of depression patients than that for spouses suggests that heritable effects highlight familial susceptibility to this disease. To what extent it also contributes to familial depression remains to be established. The anticipated gene-environment interactions with sufficient sample sizes needs to be accommodated in future etiological studies on depression.
Diseases of the myoneural junction and muscle are disabling and some are life-threatening. Recent successes in the identification of the underlying genetic mechanisms have had profound implication for their diagnostics, treatment and classification. We define familial risks for siblings who were hospitalized for or deceased from diseases of the myoneural junction and muscle. A nationwide database on diseases of the myoneural junction and muscle was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Causes of Death Register from years 1987 to 2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing to those whose siblings had no diseases of myoneural junction and muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and myotonic disorders were commonest diagnoses. The sibling risks for these disease were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease of the myoneural junction and muscle. The concordant SIRs, both siblings presenting the same disease, were 42 for myasthenia gravis, 737 for muscular dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for periodic paralysis and 209 for unspecified myopathy. Only a few discordant sibling pairs were noted. The very high overall SIRs for the diseases of the myoneural junction and muscle imply that the sporadic forms of these diseases are relatively rare and these diseases are overwhelmingly heritable.
PURPOSE: Epilepsy is a common disabling condition, with high heritability according to twin studies. Characterization of familial risks for common subtypes of epilepsy will advance the search for the heritable causes of these conditions and their underlying mechanisms. We aim at defining familial risks for siblings to be hospitalized because of epilepsy. METHODS: A nationwide ad hoc epilepsy database was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register for data on epilepsies covering the years 1987-2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing them to those whose siblings had no epilepsy. RESULTS: Among a total of 26,799 hospitalized cases, 598 affected siblings were identified with a familial SIR of 2.35; the SIR was highest at ages 0-4 years (6.82). Infantile spasms showed the highest risk for any subtype (10.45), when a co-sibling was diagnosed with any epilepsy. When both siblings were diagnosed with a concordant (same) subtype of epilepsy, the SIRs were high, i.e. 8.43 for generalized idiopathic epilepsy, 2.56 for partial epilepsy, 24.72 for status epilepticus and 24.39 for other epilepsies. Generalized idiopathic epilepsy was also associated with grand mal (4.06) and other epilepsies (7.61). The numbers of cases were small but concordant diagnoses always showing higher SIRs compared with discordant diagnoses. CONCLUSIONS: Within the limits of the present sample size, our results suggest high familial aggregation for certain subtypes of epilepsy for which distinct genetic mechanisms may underlie.