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Genetic Association Analysis of Complex Diseases Incorporating Intermediate Phenotype Information

Overview of attention for article published in PLOS ONE, October 2012
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Title
Genetic Association Analysis of Complex Diseases Incorporating Intermediate Phenotype Information
Published in
PLOS ONE, October 2012
DOI 10.1371/journal.pone.0046612
Pubmed ID
Authors

Yafang Li, Jian Huang, Christopher I. Amos

Abstract

Genetic researchers often collect disease related quantitative traits in addition to disease status because they are interested in understanding the pathophysiology of disease processes. In genome-wide association (GWA) studies, these quantitative phenotypes may be relevant to disease development and serve as intermediate phenotypes or they could be behavioral or other risk factors that predict disease risk. Statistical tests combining both disease status and quantitative risk factors should be more powerful than case-control studies, as the former incorporates more information about the disease. In this paper, we proposed a modified inverse-variance weighted meta-analysis method to combine disease status and quantitative intermediate phenotype information. The simulation results showed that when an intermediate phenotype was available, the inverse-variance weighted method had more power than did a case-control study of complex diseases, especially in identifying susceptibility loci having minor effects. We further applied this modified meta-analysis to a study of imputed lung cancer genotypes with smoking data in 1154 cases and 1137 matched controls. The most significant SNPs came from the CHRNA3-CHRNA5-CHRNB4 region on chromosome 15q24-25.1, which has been replicated in many other studies. Our results confirm that this CHRNA region is associated with both lung cancer development and smoking behavior. We also detected three significant SNPs--rs1800469, rs1982072, and rs2241714--in the promoter region of the TGFB1 gene on chromosome 19 (p = 1.46×10(-5), 1.18×10(-5), and 6.57×10(-6), respectively). The SNP rs1800469 is reported to be associated with chronic obstructive pulmonary disease and lung cancer in cigarette smokers. The present study is the first GWA study to replicate this result. Signals in the 3q26 region were also identified in the meta-analysis. We demonstrate the intermediate phenotype can potentially enhance the power of complex disease association analysis and the modified meta-analysis method is robust to incorporate intermediate phenotype or other quantitative risk factor in the analysis.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 20%
Researcher 7 18%
Student > Master 5 13%
Student > Bachelor 3 8%
Other 3 8%
Other 9 23%
Unknown 5 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 38%
Biochemistry, Genetics and Molecular Biology 7 18%
Medicine and Dentistry 7 18%
Environmental Science 2 5%
Mathematics 1 3%
Other 3 8%
Unknown 5 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 October 2012.
All research outputs
#20,171,868
of 22,684,168 outputs
Outputs from PLOS ONE
#172,805
of 193,651 outputs
Outputs of similar age
#156,406
of 176,091 outputs
Outputs of similar age from PLOS ONE
#4,128
of 4,783 outputs
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