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- Martinsson, Andreas, et al.
(författare)
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Familial Aggregation of Aortic Valvular Stenosis : A Nationwide Study of Sibling Risk
- 2017
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Background - Aortic valvular stenosis (AS) is the most common cause of cardiac valvular replacement surgery. During the last century, the pathogenesis of AS has undergone transitions in developed countries, from rheumatic heart disease to a degenerative calcific pathogenesis. Although a familial component has been described for a subset of cases with a bicuspid valve, data are limited on the overall familial aggregation of this disease. Methods and Results - Contemporary information on 6 117 263 Swedish siblings, of which 13 442 had a clinical diagnosis of AS, was collected from the nationwide Swedish Multi-Generation Register and the National Patient Register. A total of 4.8% of AS cases had a sibling history of AS. Having at least 1 sibling with AS was associated with a hazard ratio of 3.41 (95% confidence interval, 2.23-5.21) to be diagnosed with AS in an adjusted model. Individuals with >1 sibling with AS had an exceptionally high risk (hazard ratio, 32.84) but were uncommon (34 siblings from 11 sibships). In contrast, spouses of subjects with AS were only slightly more likely to be diagnosed with AS compared with subjects without spousal AS (hazard ratio 1.16 for husbands and 1.18 for wives). Conclusions - A sibling history of clinically diagnosed AS was associated with increased risk of AS. Spouses of patients with AS only had a modest risk increase, suggesting that shared adult environmental factors contribute less to the development of AS than genetic factors.
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- Zöller, Bengt, et al.
(författare)
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Body Height and Incident Risk of Venous Thromboembolism : A Cosibling Design
- 2017
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Body height has been associated with an increased risk of venous thromboembolism (VTE), but the association can be confounded with shared familial factors (genetic/environmental). A cosibling design is useful for deeper understanding about the relationship between VTE and height.METHODS AND RESULTS: From Swedish national registry databases, we used a corelative design with full siblings alongside a general Swedish population sample. A cohort of male conscripts (n=1 610 870), born in 1951 to 1992 without previous VTE, was followed from enlistment (1969-2010) until 2012. Another cohort of first-time pregnant women (n=1 093 342) from the medical birth register, without previous VTE, was followed from first pregnancy (1982-2012) until 2012. Using the Multi-Generation Register, we identified all full-sibling pairs discordant for height. This cosibling design allowed for adjustment for familial factors (genetic/environmental). Compared with the tallest women (>185 cm) and men (>190 cm), there was a graded decreased risk by lower height for both men and women. The risk was lowest in women and men with the shortest stature (<155 and <160 cm, respectively): hazard ratios=0.31 (95% confidence interval, 0.22-0.42) and 0.35 (95% confidence interval, 0.22-0.55), respectively. There was a graded association also in the cosibling design comparing siblings with varying degree of discordance for height (reference was the taller sibling): ≥10 cm difference between brothers hazard ratios=0.69 (95% confidence interval, 0.61-0.78) and sisters hazard ratios=0.65 (95% confidence interval, 0.52-0.80), respectively.CONCLUSIONS: Height is an independent predictor of VTE. The use of sibling pairs reduces the likelihood that familial confounding explains the results. The findings are important for the understanding of the pathogenesis of VTE.
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- Zöller, Bengt, et al.
(författare)
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Venous Thromboembolism Does Not Share Strong Familial Susceptibility with Ischemic Stroke: A Nationwide Family Study in Sweden.
- 2011
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 4:5, s. 484-490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Coagulation allelic variants associated with venous thromboembolism (VTE) have been suggested to be involved in the pathogenesis of ischemic stroke. This nationwide study aimed at determining whether VTE shares familial susceptibility with ischemic stroke. Method and Results-The Swedish Multigeneration Register of 0-75-year-old subjects was linked to the Swedish Hospital Discharge Register and the Cause of Death Register for the period 1987-2007. Odds ratios (OR), for VTE, and ischemic stroke were determined in two ways: odds of ischemic stroke in offspring whose parents had been diagnosed with VTE, and odds of VTE in offspring whose parents had been diagnosed with ischemic stroke. The analyses were repeated for siblings and spouses. Offspring of parents with VTE (n=25 929) were at increased risk for ischemic stroke (n=5595): OR 1.10 (95% CI 1.06-1.14). Siblings of probands with VTE (n=45 132) had no increased risk of ischemic stroke (n=1716): OR 1.05 (95% CI 1.00-1.11). Spouses of probands with VTE (n=24 106) were at increased risk for ischemic stroke (n=940): OR 1.18 (95% CI 1.10-1.27). The risks for VTE in relatives of probands with ischemic stroke were: OR 1.15, 95% CI 1.10-1.21 (offspring), OR 1.07, 95% CI 1.02-1.12 (siblings), and OR 1.21, 95% CI 1.11-1.32 (spouses). CONCLUSIONS: -Venous thromboembolism does not share strong familial susceptibility with ischemic stroke in the Swedish population. Moreover, familial non-genetic factors contribute to the observed weak familial associations. The present study suggests that it is unlikely that strong shared disease-causing mutations exist to a large extent in the Swedish population.
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