A genome-wide scan statistic framework for whole-genome sequence data analysis

被引：32

作者：

He, Zihuai ^{[1
,2
]}

Xu, Bin ^{[3
]}

Buxbaum, Joseph ^{[4
,5
,6
,7
]}

Ionita-Laza, Iuliana ^{[1
]}

机构：

[1] Columbia Univ, Dept Biostat, New York, NY 10032 USA

[2] Stanford Univ, Sch Med, Dept Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[3] Columbia Univ, Dept Psychiat, New York, NY 10032 USA

[4] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Dept Genet, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Dept Genom Sci, New York, NY 10029 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

AUTISM SPECTRUM DISORDER; DE-NOVO MUTATIONS; RARE VARIANTS; ASSOCIATIONS; ARCHITECTURE; METAANALYSIS; NETWORKS; DISEASES; ELEMENTS;

D O I：

10.1038/s41467-019-11023-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The analysis of whole-genome sequencing studies is challenging due to the large number of noncoding rare variants, our limited understanding of their functional effects, and the lack of natural units for testing. Here we propose a scan statistic framework, WGScan, to simultaneously detect the existence, and estimate the locations of association signals at genome-wide scale. WGScan can analytically estimate the significance threshold for a whole-genome scan; utilize summary statistics for a meta-analysis; incorporate functional annotations for enhanced discoveries in noncoding regions; and enable enrichment analyses using genomewide summary statistics. Based on the analysis of whole genomes of 1,786 phenotypically discordant sibling pairs from the Simons Simplex Collection study for autism spectrum disorders, we derive genome-wide significance thresholds for whole genome sequencing studies and detect significant enrichments of regions showing associations with autism in promoter regions, functional categories related to autism, and enhancers predicted to regulate expression of autism associated genes.

引用

页数：11

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