21 532 名自闭症患者的基因研究结果回报。

IF 6.6 1区 医学 Q1 GENETICS & HEREDITY
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引用次数: 0

摘要

目的:本研究旨在确定自闭症的可能致病(LP)和致病(P)基因结果,这些结果可以返还给 SPARK(SPARKforAutism.org)的参与者:SPARKforAutism.org 是美国自闭症患者的大型可再接触队列。我们还介绍了返还这些经临床证实的基因结果的过程:我们展示了 21,532 名自闭症患者及其 17,785 名父母的微阵列基因分型和外显子组测序 (ES) 结果。我们返回了 LP 和 P(美国医学遗传学会 (ACMG) 标准)拷贝数变异 (CNV)、染色体非整倍体以及与自闭症和智力障碍有关联的基因变异:我们在 1861 名自闭症患者(8.6%)中发现了 1903 个 "可返回 "的 LP/P 变异。其中 89.5%的变异参与者并不知晓。有 589 名参与者(占联系者的 53%)返回了基因诊断结果。与可返回结果的概率较高相关的特征包括认知和医学复杂特征、女性、白人(相对于非白人)以及 20 多年前确诊。我们还发现了不同谱系的自闭症患者的结果,以及具有神经精神特征但未被诊断为自闭症的传递父母的结果:结论:SPARK 提供了一个机会,可以对临床未确诊的自闭症患者的可返还结果进行评估。SPARK 还提供了大规模返回行为状况遗传结果的实际经验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Return of genetic research results in 21,532 individuals with autism

Purpose

The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings.

Methods

We present results from microarray genotyping and exome sequencing of 21,532 individuals with autism and 17,785 of their parents. We returned LP and P (American College of Medical Genetics criteria) copy-number variants, chromosomal aneuploidies, and variants in genes with strong evidence of association with autism and intellectual disability.

Results

We identified 1903 returnable LP/P variants in 1861 individuals with autism (8.6%). 89.5% of these variants were not known to participants. The diagnostic genetic result was returned to 589 participants (53% of those contacted). Features associated with a higher probability of having a returnable result include cognitive and medically complex features, being female, being White (versus non-White) and being diagnosed more than 20 years ago. We also find results among autistics across the spectrum, as well as in transmitting parents with neuropsychiatric features but no autism diagnosis.

Conclusion

SPARK offers an opportunity to assess returnable results among autistic people who have not been ascertained clinically. SPARK also provides practical experience returning genetic results for a behavioral condition at a large scale.

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来源期刊
Genetics in Medicine
Genetics in Medicine 医学-遗传学
CiteScore
15.20
自引率
6.80%
发文量
857
审稿时长
1.3 weeks
期刊介绍: Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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