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特定病因死亡率的遗传度:应用于1870 - 1930年出生的丹麦双胞胎呼吸系统疾病死亡率的相关伽马脆弱模型

The heritability of cause-specific mortality: a correlated gamma-frailty model applied to mortality due to respiratory diseases in Danish twins born 1870-1930.

作者信息

Wienke Andreas, Holm Niels V, Christensen Kaare, Skytthe Axel, Vaupel James W, Yashin Anatoli I

机构信息

Max Planck Institute for Demographic Research, Rostock, Germany.

出版信息

Stat Med. 2003 Dec 30;22(24):3873-87. doi: 10.1002/sim.1669.

Abstract

The genetic influence on susceptibility to diseases of the respiratory system and all-cause mortality was studied using data for identical (MZ) and fraternal (DZ) twins. Data from the Danish Twin Register include 1344 MZ and 2411 DZ male twin pairs and 1470 MZ and 2730 DZ female twin pairs born between 1870 and 1930, where both individuals were alive on 1 011943. We used the correlated gamma-frailty model. Proportions of variance in frailty attributable to genetic and environmental factors were assessed using the structural equation model approach. For all-cause mortality the correlation coefficients of frailty for MZ twins tend to be higher than for DZ twins. For mortality with respect to respiratory diseases this effect was only seen in females, whereas males showed the opposite effect. Five standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting biometric model heritability for cause of death was found to be 0.58 (0.07) for all-cause mortality (AE-model) and zero for diseases of the respiratory system for males. Heritability was 0.63 (0.11) for all-cause mortality (DE-model) and 0.18 (0.09) for diseases of the respiratory system (DE-model) for females. The analysis confirms the presence of a strong genetic influence on individual frailty associated with all-cause mortality. For respiratory diseases, no genetic influence was found in males and only weak genetic influence in females. The nature of genetic influences on frailty with respect to all-cause mortality is probably additive in males and dominant in females, whereas for frailty with respect to deaths caused by respiratory diseases in females, there are genetic factors present which are caused by dominance. Environmental influences are non-shared with exception of frailty with respect to respiratory diseases in males, where the shared environment plays an important role.

摘要

利用同卵(MZ)和异卵(DZ)双胞胎的数据,研究了遗传因素对呼吸系统疾病易感性和全因死亡率的影响。丹麦双胞胎登记处的数据包括1870年至1930年间出生的1344对MZ男性双胞胎和2411对DZ男性双胞胎,以及1470对MZ女性双胞胎和2730对DZ女性双胞胎,其中两人在1943年1月1日时均在世。我们使用了相关伽马脆弱模型。采用结构方程模型方法评估了遗传和环境因素在脆弱性方面的方差比例。对于全因死亡率,MZ双胞胎脆弱性的相关系数往往高于DZ双胞胎。对于呼吸系统疾病死亡率,这种影响仅在女性中可见,而男性则表现出相反的影响。对数据拟合了五个标准生物统计学模型,以评估遗传和环境因素对死亡率的影响程度和性质。使用最佳拟合生物统计学模型,发现全因死亡率(AE模型)的死亡原因遗传度为0.58(0.07),男性呼吸系统疾病的遗传度为零。女性全因死亡率(DE模型)的遗传度为0.63(0.11),呼吸系统疾病(DE模型)的遗传度为0.18(0.09)。分析证实,遗传因素对与全因死亡率相关的个体脆弱性有强烈影响。对于呼吸系统疾病,未发现男性有遗传影响,女性仅有微弱的遗传影响。遗传因素对全因死亡率脆弱性的影响性质在男性中可能是加性的,在女性中是显性的,而对于女性呼吸系统疾病导致的死亡脆弱性,存在由显性引起的遗传因素。除男性呼吸系统疾病脆弱性外,环境影响是不共享的,在男性呼吸系统疾病脆弱性方面,共享环境起着重要作用。

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