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一项关于酒精使用障碍的瑞典全国性扩展收养研究。

An extended Swedish national adoption study of alcohol use disorder.

作者信息

Kendler Kenneth S, Ji Jianguang, Edwards Alexis C, Ohlsson Henrik, Sundquist Jan, Sundquist Kristina

机构信息

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond2Department of Psychiatry, Virginia Commonwealth University, Richmond3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richm.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

出版信息

JAMA Psychiatry. 2015 Mar;72(3):211-8. doi: 10.1001/jamapsychiatry.2014.2138.

Abstract

IMPORTANCE

Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors.

OBJECTIVE

To determine to what extent genetic and environmental factors contribute to the risk for AUD.

DESIGN, SETTING, AND PARTICIPANTS: Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989 and 107,696 offspring of not-lived-with parents and stepparents, respectively (born 1960-1993).

MAIN OUTCOMES AND MEASURES

Alcohol use disorder recorded in medical, legal, or pharmacy registry records.

RESULTS

Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders.

CONCLUSIONS AND RELEVANCE

Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

摘要

重要性

酒精使用障碍(AUD)在家族中具有很强的遗传性。目前尚不清楚AUD的跨代传播在多大程度上是由遗传因素还是环境因素导致的。

目的

确定遗传和环境因素在多大程度上导致AUD风险。

设计、设置和参与者:对瑞典8个公开数据登记处的被收养者、其生物学和收养亲属、继子女以及来自继家庭和非共同生活家庭的子女及其父母进行随访。在这项队列研究中,通过潜在类别分析评估AUD的亚型。共有18115名被收养者(出生于1950 - 1993年),以及分别为171989名和107696名非共同生活父母和继父母的子女(出生于1960 - 1993年)。

主要结局和测量指标

医疗、法律或药房登记记录中记录的酒精使用障碍。

结果

生物学父母患AUD(优势比,1.46;95%置信区间,1.29 - 1.66)、兄弟姐妹患AUD(优势比,1.94;95%置信区间,1.55 - 2.44)以及收养父母患AUD(优势比,1.40;95%置信区间,1.09 - 1.80)均能显著预测被收养者患酒精使用障碍。由生物学和收养亲属创建的遗传和环境风险指数对被收养者患AUD的易感性具有累加作用。分别对非共同生活父母和继父母的研究重复并扩展了来自生物学和收养亲属的结果。这些家庭中的多变量模型表明,非共同生活父母的AUD、药物滥用、精神疾病和犯罪以及继父母的AUD、药物滥用、犯罪和过早死亡均能显著预测子女患AUD。对患有AUD的被收养者和非共同生活父母的子女进行潜在类别分析,发现了3种AUD类别,其特征分别为:(1)女性占优势且精神疾病发生率高;(2)轻度非复发性症状;(3)早发性复发、药物滥用和犯罪。这些类别在其非共同生活父母患各种疾病的风险模式中具有独特的遗传特征,并且在记录的情绪障碍发生率上存在显著差异。

结论及意义

AUD的亲子传播是由遗传和环境因素共同导致的。AUD的遗传风险既反映了对AUD的特定易感性,也反映了对其他外化性障碍的易感性。环境风险既反映了父母精神病理学特征,也反映了养育环境的其他方面。酒精使用障碍是一种异质性综合征,潜在类别分析得出了有意义的亚型,并通过生物学父母的疾病模式和特定的精神共病情况得到了验证。普通人群包含信息丰富的家庭组合,在阐明亲子相似性的来源方面可以补充更传统的收养设计。

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