南方科技大学知识苑(SUSTech KC): Integration of rare expression outlier-associated variants improves polygenic risk prediction

题名	Integration of rare expression outlier-associated variants improves polygenic risk prediction
作者	Smail，Craig 1,2; Ferraro，Nicole M.1; Hui，Qin 3,4; Durrant，Matthew G.5; Aguirre，Matthew 1; Tanigawa，Yosuke 1; Keever-Keigher，Marissa R.2; Rao，Abhiram S.6,7; Justesen，Johanne M.1; Li，Xin 8; Gloudemans，Michael J.1; Assimes，Themistocles L.9,10; Kooperberg，Charles 11; Reiner，Alexander P.12; Huang，Jie13 ; O'Donnell，Christopher J.14,15,16; Sun，Yan V.3,4; Rivas，Manuel A.1; Montgomery，Stephen B.5,6
通讯作者	Smail，Craig; Montgomery，Stephen B.
发表日期	2022-06-02
DOI	10.1016/j.ajhg.2022.04.015
发表期刊	AMERICAN JOURNAL OF HUMAN GENETICS 影响因子和分区
ISSN	0002-9297
EISSN	1537-6605
卷号	109 期号:6页码:1055-1064
摘要	Polygenic risk scores (PRSs) quantify the contribution of multiple genetic loci to an individual's likelihood of a complex trait or disease. However, existing PRSs estimate this likelihood with common genetic variants, excluding the impact of rare variants. Here, we report on a method to identify rare variants associated with outlier gene expression and integrate their impact into PRS predictions for body mass index (BMI), obesity, and bariatric surgery. Between the top and bottom 10%, we observed a 20.8% increase in risk for obesity (p = 3 x 10(-14)), 62.3% increase in risk for severe obesity (p = 1 x 10(-6)), and median 5.29 years earlier onset for bariatric surgery (p = 0.008), as a function of expression outlier-associated rare variant burden when controlling for common variant PRS. We show that these predictions were more significant than integrating the effects of rare protein-truncating variants (PTVs), observing a mean 19% increase in phenotypic variance explained with expression outlier-associated rare variants when compared with PTVs (p = 2 x 10(-15)). We replicated these findings by using data from the Million Veteran Program and demonstrated that PRSs across multiple traits and diseases can benefit from the inclusion of expression outlier-associated rare variants identified through population-scale transcriptome sequencing.
相关链接	[来源记录]
收录类别	SCI
语种	英语
重要成果	NI论文
学校署名	其他
资助项目	NIH[
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000821957400006
出版者	CELL PRESS
ESI学科分类	MOLECULAR BIOLOGY & GENETICS
Scopus记录号	2-s2.0-85131050937
来源库	Web of Science
引用统计	被引频次[WOS]：9
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/336247
专题	南方科技大学医学院_公共卫生及应急管理学院
作者单位	1.Department of Biomedical Data Science,Stanford University School of Medicine,Stanford,United States 2.Genomic Medicine Center,Children's Mercy Research Institute and Children's Mercy Kansas City,Kansas City,United States 3.Atlanta VA Health Care System,Decatur,United States 4.Department of Epidemiology,Emory University Rollins School of Public Health,Atlanta,United States 5.Department of Genetics,Stanford University School of Medicine,Stanford,United States 6.Department of Pathology,Stanford University School of Medicine,Stanford,United States 7.Department of Bioengineering,Stanford University,Stanford,United States 8.CAS Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Shanghai,China 9.Palo Alto VA Health Care System,Palo Alto,United States 10.Division of Cardiovascular Medicine,Department of Medicine,Stanford University School of Medicine,Stanford,United States 11.Public Health Sciences Division,Fred Hutchinson Cancer Center,Seattle,United States 12.Department of Epidemiology,University of Washington,Seattle,United States 13.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,Guangdong,China 14.Boston VA Health Care System,Boston,United States 15.Division of Cardiology,Department of Medicine,Harvard Medical School,Boston,United States 16.Division of Cardiology,Department of Medicine,Brigham Women's Hospital,Boston,United States
推荐引用方式 GB/T 7714	Smail，Craig,Ferraro，Nicole M.,Hui，Qin,et al. Integration of rare expression outlier-associated variants improves polygenic risk prediction[J]. AMERICAN JOURNAL OF HUMAN GENETICS,2022,109(6):1055-1064.
APA	Smail，Craig.,Ferraro，Nicole M..,Hui，Qin.,Durrant，Matthew G..,Aguirre，Matthew.,...&Montgomery，Stephen B..(2022).Integration of rare expression outlier-associated variants improves polygenic risk prediction.AMERICAN JOURNAL OF HUMAN GENETICS,109(6),1055-1064.
MLA	Smail，Craig,et al."Integration of rare expression outlier-associated variants improves polygenic risk prediction".AMERICAN JOURNAL OF HUMAN GENETICS 109.6(2022):1055-1064.

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