Summary. Background: Venous thromboembolism (VTE) is postulated as a complex disease, but the heritability and mode of inheritance are uncertain. Objective: To determine if VTE (i) segregates in families; (ii) is attributable to inheritance, shared environment, or both; and (iii) the possible mode of inheritance. Patients and methods: In a family-based study of relatives from 751 probands (60% female) with objectively diagnosed VTE (without cancer), we performed complex segregation analyses corrected for mode of ascertainment, considering agespecific, non-gender-and gender-specific liability classes under Mendelian and non-Mendelian assumptions. We tested 12 models categorized into four model sets: (i) sporadic (assumes no genetic effect); (ii) Mendelian inheritance of a major gene (including dominant, additive, recessive or codominant classes); (iii) mixed model (Mendelian inheritance including the same four classes plus the effect of polygenes); and (iv) nonMendelian. Results: Among the 16 650 relatives, 753 (48% female) were affected with VTE, of whom 62% were first-degree relatives. The sporadic model was rejected in both non-genderand gender-specific liability class analyses. Among the remaining gender-specific models, the unrestricted (non-Mendelian) inheritance model was favored with an estimated heritability of 0.52. Among the Mendelian models, the dominant mixed model was preferred, with an estimated heritability and major disease allele frequency of 0.62 and 0.25, respectively, suggesting an effect of several minor genes. Conclusion: A multifactorial non-Mendelian inheritance model was favored as the cause for VTE, while a model postulating a purely environmental cause was rejected. VTE is probably a result of multigenic action as well as environmental exposures.
Background-Multiple B-type natriuretic peptide (BNP) fragments circulate in patients with heart failure (HF) but the types and relative quantities, particularly in relation to bioactive BNP 1-32, remain poorly defined. The purpose of the study was to relate clinically available BNP values with quantitative information on the concentration of pre-secretion and post-processed fragments of BNP detected by mass spectrometry. Methods and Results-Seventy Class I-IV patients were prospectively enrolled with blood drawn into tubes containing a preservative to protect against BNP degradation.
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