基因大数据的集成分析

doi:10.11959/j.issn.2096-0271.2019033

摘要/Abstract

摘要：

随着生物科技（如基因芯片和测序技术）的飞速发展，全世界已经积累了海量的数据。有效地整合和集成多层面和多维度的基因大数据，对于全方位解析从遗传变异到疾病发生的整个因果链条具有关键作用，可为个性化、精准医疗服务奠定科学的基础。从3个方面对基因大数据的集成分析进行综述：检测风险位点及其功能分析、基因多效性的分析、基于孟德尔随机化的因果推断。进一步结合具体的应用案例进行了阐述，最后对基因大数据的集成分析研究进行了总结以及展望。

关键词: GWAS, 集成分析, 多基因效应, 基因多效性, 孟德尔随机化

Abstract:

With the rapid development of bio-technology (e.g.,genotyping chip and sequencing),world-wide researchers have accumulated massive data sets at different levels.Integrative analysis of multi-layered genomic data can greatly contribute to the completion of causal chain from genetic variants to phenotype variations,laying a scientific foundation for personalized and precise medicine.The integrative analysis from the following three aspects mainly reviewed:identification of causal variants and their functional annotation,pleiotropy in human complex traits,Mendelian randomization forcausal inference between phenotypes,and several case studies were provided.Finally,the importance of integrative analysis in genomic data for precision medicine was highlighted.

Key words: GWAS, integrative analysis, polygenicity, pleiotropy, Mendelian randomization

中图分类号:

TP391

胡湘红,彭衡,杨灿,张纵辉,万翔,罗智泉. 基因大数据的集成分析[J]. 大数据, 2019, 5(4): 67-88.

Xianghong HU,Heng PENG,Can YANG,Tsunghui CHANG,Xiang WAN,Zhiquan LUO. Integrative analysis for big data in genomics[J]. Big Data Research, 2019, 5(4): 67-88.

图/表 11

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表1

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表2

复杂性状和疾病的GWAS数据来源"

类别	性状或疾病	中文名称	英文名称	参考文献
人体测量指标	BMI	体重指数	body mass index	[59]
	BFP	体脂百分比	body fat percentage	[60]
	Hip	臀围	hip circumference	[61]
	WC	腰围	waist circumference	[61]
	WHR	腰臀比	waist hip ratio	[61]
	BL	出生长度	birth length	[62]
	BW	出生体重	birth weight	[63]
	CO	童年肥胖	childhood obesity	[64]
	IHC	婴儿头围	infant head circumference	[65]
	Height	身高	height	[66]
与心血管相关的指标	DBP	舒张压	diastolic blood pressure	[67]
	HTN	高血压	hypertension	[67]
	MAP	平均动脉压	mean arterial pressure	[67]
	PP	脉压	pulse pressure	[67]
	SBP	收缩压	systolic blood pressure	[67]
	PVD	周边血管疾病	peripheral vascular disease	[51]
	CAD	冠心病	coronary artery disease	[68]
	HR	心率	heart rate	[69]
	HRV_Pvrsa_Hf	心率变异性指标一	heart rate variability index 1	[70]
	HRV_Rmssd	心率变异性指标二	heart rate variability index 2	[70]
	HR_Sdnn	心率变异性指标三	heart rate variability index 3	[70]
免疫系统疾病	AD	特应性皮炎	atopic dermatitis	[71]
	Crohn_Disease	克罗恩病	Crohn disease	[72]
	Celiac_Disease	腹腔疾病	celiac disease	[73]
	Eczema	湿疹	eczema	[71]
	IBD	炎症性肠病	inflammatory bowel diseases	[72]
	MS	多发性硬化症	multiple sclerosis	[74]
	PBC	原发性胆汁性肝硬化	primary biliary cirrhosis	[75]
	RA	类风湿关节炎	rheumatoid arthritis	[76]
	UC	溃疡性结肠炎	ulcerative colitis	[72]
	T1D	Ⅰ型糖尿病	type 1 diabetes	[77]
	SLE	系统性红斑狼疮	systemic lupus erythematosus	[78]
代谢类疾病	T2D	Ⅱ型糖尿病	type2 diabetes	[79]
	ANM	更年期年龄	age at natural menopause	[80]
	Dyslipid	脂类代谢异常	dyslipidemia	[51]
	eGFR	肾小球滤过率	estimated glomerular filtration rate	[81]
	FPI	空腹胰岛素原	fasting proinsulin	[82]
	uACR	尿蛋白/肌酐比值	urinary albumin to cretinine ratio	[83]
	AM	初潮年龄	age at menarche	[84]
	FI	空腹胰岛素	fasting insulin	[85]
神经系统疾病	AD	阿尔茨海默症	alzheimer’s disease	[86]
	ALS	肌萎缩侧索硬化症	amyotrophic lateral sclerosis	[87]
	MD	黄斑变性	macular degeneration	[51]
	Parkinson	帕金森综合征	Parkinson’s disease	[88]
精神疾病	Angst	焦虑症	angst	[89]
	BIP	双相情感障碍症	bipolar disorder	[90]
	ADHD	多动症	attention deficit hyperactivity disorder	[55]
	ASD	自闭症谱系障碍	autism spectrum disorder	[55]
	PTSD	创伤后应激障碍	post-traumatic stress disorder	[91]
	SCZ	精神分裂症	schizophrenia	[55]
	Stress	压力	stress	[51]
	Depress	抑郁	depress	[51]
	AN	神经性厌食症	anorexia nervosa	[92]
	CAB	童年期攻击行为	childhood aggressive behaviour	[93]
	Loneliness	孤独	loneliness	[94]
	OCD	强迫症	obsessive compulsive disorder	[95]
	MDD	重度抑郁症	major depressive disorder	[95]

表2

图8

图9

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疾病	与另一性状同时分析	引入功能型数据	显著的变异位点数（FDR< 0.05）/个
神经质	否	否	1 623
重度抑郁症	否	否	322
神经质	否	是	1 653
重度抑郁症	否	是	353
神经质	是	否	3 207
重度抑郁症	是	否	3 739
神经质	是	是	3 281
重度抑郁症	是	是	3 818