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Evaluating the impact of non-random mating: psychiatric outcomes among the offspring of pairs diagnosed with Schizophrenia and Bipolar Disorder
Biological Psychiatry ( IF 10.6 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.biopsych.2019.06.025
Ashley E Nordsletten 1 , Gustaf Brander 2 , Henrik Larsson 3 , Paul Lichtenstein 3 , James J Crowley 4 , Patrick F Sullivan 5 , Naomi R Wray 6 , David Mataix-Cols 2
Affiliation  

BACKGROUND Nonrandom mating has been shown for psychiatric diagnoses, with hypothesized-but not quantified-implications for offspring liability. This national cohort study enumerated the incidence of major psychiatric disorders among the offspring of parent pairs affected with schizophrenia (SCZ) and/or bipolar disorder (BIP) (i.e., dual-affected pairs). METHODS Participants were all Swedish residents alive or born between 1968 and 2013 (n = 4,255,196 unique pairs and 8,343,951 offspring). Offspring with dual-affected, single-affected, and unaffected parents were followed (1973-2013) for incidence of broad psychiatric disorders. Primary outcomes included hazard ratio (HR) and cumulative incidence for SCZ and BIP in the offspring. Additional outcomes included any neuropsychiatric, anxiety, depressive, personality, or substance use disorders. Cumulative incidences of SCZ and BIP were used to inform heritability models for these disorders. RESULTS Hazards were highest within disorder (e.g., offspring of dual-SCZ pairs had sharply raised hazards for SCZ [HR = 55.3]); however, they were significantly raised for all diagnoses (HR range = 2.89-11.84). Incidences were significantly higher for the majority of outcomes, with 43.4% to 48.5% diagnosed with "any" disorder over follow-up. Risks were retained, with modest attenuations, for the offspring of heterotypic pairs. The estimated heritability of liability for SCZ (h2 = 0.62, 95% confidence interval = 0.55-0.70) and BIP (h2 = 0.52, 95% confidence interval = 0.46-0.58) did not differ significantly from estimates derived from single-affected parents. CONCLUSIONS Risks for a broad spectrum of psychiatric diagnoses are significantly raised in the offspring of dual-affected parents, in line with expectations from a polygenic model of liability to disease risk. How these risks may contribute to population maintenance of these disorders is considered.

中文翻译:

评估非随机交配的影响:被诊断患有精神分裂症和双相情感障碍的配对的后代的精神病结果

背景 非随机交配已被证明用于精神病学诊断,对后代责任具有假设但未量化的影响。这项全国性队列研究列举了受精神分裂症 (SCZ) 和/或双相情感障碍 (BIP) 影响的父母对(即双重影响对)的后代中主要精神疾病的发生率。方法 参与者是所有在 1968 年至 2013 年期间活着或出生的瑞典居民(n = 4,255,196 对独特的配对和 8,343,951 个后代)。对双亲、单亲和未受影响的父母的后代进行随访(1973-2013 年),了解广泛精神疾病的发生率。主要结果包括后代 SCZ 和 BIP 的风险比 (HR) 和累积发生率。其他结果包括任何神经精神、焦虑、抑郁、人格或物质使用障碍。SCZ 和 BIP 的累积发生率用于为这些疾病的遗传模型提供信息。结果 疾病中的危害最高(例如,双 SCZ 对的后代对 SCZ 的危害急剧增加 [HR = 55.3]);然而,对于所有诊断,它们都显着升高(HR 范围 = 2.89-11.84)。大多数结果的发生率显着更高,43.4% 至 48.5% 在随访期间被诊断为“任何”疾病。对于异型对的后代,风险被保留,但适度减弱。SCZ (h2 = 0.62, 95% 置信区间 = 0.55-0.70) 和 BIP (h2 = 0.52, 95% 置信区间 = 0.46-0.58) 的估计遗传力与来自单亲父母的估计值没有显着差异。结论 双重影响父母的后代中广泛的精神病诊断风险显着增加,这与疾病风险责任的多基因模型的预期一致。考虑这些风险如何促进这些疾病的人群维持。
更新日期:2020-02-01
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