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      Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

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          Abstract

          Objective

          Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors.

          Design

          This study is a twin cohort study.

          Methods

          National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and vice-versa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models.

          Results

          Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5–15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2–15.1) and 1.7 (95% CI: 0.7–4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis.

          Conclusions

          Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets.

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          Most cited references44

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          External review and validation of the Swedish national inpatient register

          Background The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
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            The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research

            Swedish health care and national health registers are dependent on the presence of a unique identifier. This paper describes the Swedish personal identity number (PIN) and explores ethical issues of its use in medical research. A ten-digit-PIN is maintained by the National Tax Board for all individuals that have resided in Sweden since 1947. Until January 2008, an estimated 75,638 individuals have changed PIN. The most common reasons for change of PIN are incorrect recording of date of birth or sex among immigrants or newborns. Although uncommon, change of sex always leads to change of PIN since the PIN is sex-specific. The most common reasons for re-use of PIN (n = 15,887), is when immigrants are assigned a PIN that has previously been assigned to someone else. This is sometimes necessary since there is a shortage of certain PIN combinations referring to dates of birth in the 1950s and 1960s. Several ethical issues can be raised pro and con the use of PIN in medical research. The Swedish PIN is a useful tool for linkages between medical registers and allows for virtually 100% coverage of the Swedish health care system. We suggest that matching of registers through PIN and matching of national health registers without the explicit approval of the individual patient is to the benefit for both the individual patient and for society.
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              The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months.

              To describe the content and potentials of the new Swedish national register on prescribed and dispensed medicines. The Swedish Prescribed Drug Register contains information about age, sex and unique identifier of the patient as well as the prescriber's profession and practice. Information regarding drug utilization and expenditures for prescribed drugs in the entire Swedish population was extracted from the first six months July-December 2005 and compared with total drug sales in the country including OTC and hospital use. The total quantity of drugs sold in Sweden was 2666 million DDDs, corresponding to 1608 DDD/1000 inhabitants daily. The total expenditures were 1.6 billion Euro. The prescribed drugs, included in the register, accounted for 84% of the total utilization and 77% of the total expenditures. About half of all men and two-thirds of all women in the country purchased drugs. The proportion increased by age. The most common drugs for chronic treatment were diuretics among women (8.8% of the population) and antithrombotic agents among men (7.6%). Psychotropic drugs, corticosteroids and analgesics were more common among women, while men used antithrombotic agents, antidiabetic drugs, lipid lowering agents and ACE inhibitors to a greater extent. The new register provides valuable data on exposure to drugs and is useful to study patterns of drug utilization. The possibilities for record linkage to other health registers gives from an international perspective good opportunities to explore drug and disease associations and the risks, benefits, effectiveness and health economical effects of drug use.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur J Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                07 April 2022
                01 June 2022
                : 186
                : 6
                : 677-685
                Affiliations
                [1 ]Department of Molecular Medicine and Surgery , Karolinska Institutet, Stockholm, Sweden
                [2 ]Department of Medicine , Karlstad Central Hospital, Karlstad, Sweden
                [3 ]Department of Medical Epidemiology and Biostatistics , Karolinska Institutet, Stockholm, Sweden
                [4 ]Institute of Medicine , University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
                [5 ]National Diabetes Register , Centre of Registers, Gothenburg, Sweden
                [6 ]Center for Molecular Medicine , Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden
                [7 ]Department of Endocrinology , Karolinska University Hospital, Stockholm, Sweden
                [8 ]K.G. Jebsen Center for Autoimmune Diseases , University of Bergen, Bergen, Norway
                Author notes
                Correspondence should be addressed to J Skov; Email: jakob.skov@ 123456regionvarmland.se
                Author information
                http://orcid.org/0000-0002-3738-1367
                Article
                EJE-22-0025
                10.1530/EJE-22-0025
                9175555
                36321757
                53188a0e-5a0f-4fcc-b6c9-be33cfeabf12
                © The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 11 January 2022
                : 07 April 2022
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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