Disease Risk Factors Identified Through Shared Genetic Architecture and Electronic Medical Records

被引：38

作者：

Li, Li ^{[1
,2
]}

Ruau, David J. ^{[1
,2
]}

Patel, Chirag J. ^{[1
,2
,3
]}

Weber, Susan C. ^{[4
]}

Chen, Rong ^{[1
,5
]}

Tatonetti, Nicholas P. ^{[6
,7
]}

Dudley, Joel T. ^{[8
]}

Butte, Atul J. ^{[1
,2
]}

机构：

[1] Stanford Univ, Dept Pediat, Sch Med, Div Syst Med, Stanford, CA 94305 USA

[2] Lucile Packard Childrens Hosp, Palo Alto, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA

[4] Stanford Univ, Stanford Ctr Clin Informat, Sch Med, Stanford, CA 94305 USA

[5] Personalis Inc, Menlo Pk, CA 94025 USA

[6] Columbia Univ, Dept Biomed Informat, Columbia Initiat Syst Biol, New York, NY 10027 USA

[7] Columbia Univ, Dept Med, New York, NY 10027 USA

[8] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2014年 / 6卷 / 234期

关键词：

GENOME-WIDE ASSOCIATION; LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE-A2; OBSTRUCTIVE PULMONARY-DISEASE; CORONARY-ARTERY-DISEASE; BASAL-CELL CARCINOMA; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; BLOOD-PRESSURE; METABOLIC SYNDROME; LUNG-CANCER;

D O I：

10.1126/scitranslmed.3007191

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Genome-wide association studies have identified genetic variants for thousands of diseases and traits. We evaluated the relationships between specific risk factors (for example, blood cholesterol level) and diseases on the basis of their shared genetic architecture in a comprehensive human disease-single-nucleotide polymorphism association database (VARIMED), analyzing the findings from 8962 published association studies. Similarity between traits and diseases was statistically evaluated on the basis of their association with shared gene variants. We identified 120 disease-trait pairs that were statistically similar, and of these, we tested and validated five previously unknown disease-trait associations by searching electronic medical records (EMRs) from three independent medical centers for evidence of the trait appearing in patients within 1 year of first diagnosis of the disease. We validated that the mean corpuscular volume is elevated before diagnosis of acute lymphoblastic leukemia; both have associated variants in the gene IKZF1. Platelet count is decreased before diagnosis of alcohol dependence; both are associated with variants in the gene C12orf51. Alkaline phosphatase level is elevated in patients with venous thromboembolism; both share variants in ABO. Similarly, we found that prostate-specific antigen and serum magnesium levels were altered before the diagnosis of lung cancer and gastric cancer, respectively. Disease-trait associations identify traits that could serve as future prognostics, if validated through EMR and sub-sequent prospective trials.

引用

页数：12

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