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基于 4408646 对全同胞和半同胞以及 333748 例病例和对照的家族数据和遗传数据,对 8 种精神障碍的遗传影响进行研究。

Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls.

机构信息

Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.

Department of Psychiatry,Washington University in Saint Louis School of Medicine,Saint Louis, MO,USA.

出版信息

Psychol Med. 2019 May;49(7):1166-1173. doi: 10.1017/S0033291718002039. Epub 2018 Sep 17.


DOI:10.1017/S0033291718002039
PMID:30221610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6421104/
Abstract

BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50. CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

摘要

背景:大多数研究强调遗传因素对精神疾病的贡献。然而,遗传度的估计取决于所研究的人群、诊断工具和研究设计,每个设计都有其内在的假设、优势和偏差。我们旨在检验两种强大的、最先进的研究设计在八种精神疾病中的遗传度估计值的同质性。

方法:我们根据瑞典同胞的数据(N=4408646 名全同胞和半同胞),以及基于测量基因型的八个样本的汇总数据(N=125533 例病例和 208215 例对照)评估遗传度。所有数据均基于标准诊断标准。研究了八种精神疾病:(1)酒精依赖(AD),(2)神经性厌食症,(3)注意力缺陷/多动障碍(ADHD),(4)自闭症谱系障碍,(5)双相情感障碍,(6)重性抑郁障碍,(7)强迫症(OCD)和(8)精神分裂症。

结果:来自同胞数据的遗传度估计值从重度抑郁症的 0.30 到 ADHD 的 0.80 不等。基于测量基因型的估计值较低,范围从 AD 的 0.10 到 OCD 的 0.28,但具有统计学意义,并与基于全国同胞的估计值呈正相关(0.19)。当从数据中去除 OCD 时,相关性增加到 0.50。

结论:鉴于每种研究设计的独特性质,这八种精神疾病的一致发现表明遗传度估计值在不同方法中是稳健的。这些发现还突出了精神疾病之间遗传和环境影响的巨大差异,为病因学精神疾病研究提供了未来的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ac/6498784/93c293cafd29/S0033291718002039_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ac/6498784/93c293cafd29/S0033291718002039_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ac/6498784/93c293cafd29/S0033291718002039_fig1.jpg

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本文引用的文献

[1]
Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits.

Nat Genet. 2018-4-26

[2]
Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium.

Biol Psychiatry. 2017-9-21

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Nat Genet. 2017-8-30

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BMC Psychiatry. 2017-6-30

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Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition.

Mol Psychiatry. 2017-6-6

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Nat Genet. 2017-1

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JAMA Psychiatry. 2016-11-1

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JAMA Psychiatry. 2016-4

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Disease and Polygenic Architecture: Avoid Trio Design and Appropriately Account for Unscreened Control Subjects for Common Disease.

Am J Hum Genet. 2016-2-4

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