Abstract
Many complex diseases, such as psychiatric and behavioral disorders, are commonly characterized through various measurements that reflect physical, behavioral and psychological aspects of diseases. While it remains a great challenge to find a unified measurement to characterize a disease, the available multiple phenotypes can be analyzed jointly in the genetic association study. Simultaneously testing these phenotypes has many advantages, including considering different aspects of the disease in the analysis, and utilizing correlated phenotypes to improve the power of detecting disease-associated variants. Furthermore, complex diseases are likely caused by the interplay of multiple genetic variants through complicated mechanisms. Considering gene-gene interactions in the joint association analysis of complex diseases could further increase our ability to discover genetic variants involving complex disease pathways. In this article, we propose a stepwise U-test for joint association analysis of multiple loci and multiple phenotypes. Through simulations, we demonstrated that testing multiple phenotypes simultaneously could attain higher power than testing one single phenotype at a time, especially when there are shared genes contributing to multiple phenotypes. We also illustrated the proposed method with an application to Nicotine Dependence (ND), using datasets from the Study of Addition, Genetics and Environment (SAGE). The joint analysis of three ND phenotypes identified two SNPs, rs10508649 and rs2491397, and reached a nominal P-value of 3.79e-13. The association was further replicated in two independent datasets with P-values of 2.37e-05 and 7.46e-05.
Keywords: Pleiotropy, Nicotine dependence, Population-based association studies.
Current Genomics
Title:Detecting Gene-Gene Interactions Associated with Multiple Complex Traits with U-Statistics
Volume: 17 Issue: 5
Author(s): Ming Li, Changshuai Wei, Yalu Wen, Tong Wang and Qing Lu
Affiliation:
Keywords: Pleiotropy, Nicotine dependence, Population-based association studies.
Abstract: Many complex diseases, such as psychiatric and behavioral disorders, are commonly characterized through various measurements that reflect physical, behavioral and psychological aspects of diseases. While it remains a great challenge to find a unified measurement to characterize a disease, the available multiple phenotypes can be analyzed jointly in the genetic association study. Simultaneously testing these phenotypes has many advantages, including considering different aspects of the disease in the analysis, and utilizing correlated phenotypes to improve the power of detecting disease-associated variants. Furthermore, complex diseases are likely caused by the interplay of multiple genetic variants through complicated mechanisms. Considering gene-gene interactions in the joint association analysis of complex diseases could further increase our ability to discover genetic variants involving complex disease pathways. In this article, we propose a stepwise U-test for joint association analysis of multiple loci and multiple phenotypes. Through simulations, we demonstrated that testing multiple phenotypes simultaneously could attain higher power than testing one single phenotype at a time, especially when there are shared genes contributing to multiple phenotypes. We also illustrated the proposed method with an application to Nicotine Dependence (ND), using datasets from the Study of Addition, Genetics and Environment (SAGE). The joint analysis of three ND phenotypes identified two SNPs, rs10508649 and rs2491397, and reached a nominal P-value of 3.79e-13. The association was further replicated in two independent datasets with P-values of 2.37e-05 and 7.46e-05.
Export Options
About this article
Cite this article as:
Li Ming, Wei Changshuai, Wen Yalu, Wang Tong and Lu Qing, Detecting Gene-Gene Interactions Associated with Multiple Complex Traits with U-Statistics, Current Genomics 2016; 17 (5) . https://dx.doi.org/10.2174/1389202917666160513100946
DOI https://dx.doi.org/10.2174/1389202917666160513100946 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Improvement of Nutritional Qualities of Fermented Kernels of Wild Legume Canavalia cathartica by Rhizopus oligosporus
Current Biochemical Engineering (Discontinued) Single Vial Kit Formulation of Technetium-99m-L,L -Ethylene Dicysteine: Its Characterisation, Biodistribution and Comparison with Commercially Available 99mTc-L, L-EC Kits
Current Radiopharmaceuticals Medical Image Processing Technology for Diagnosing and Treating Cancers
Recent Patents on Biomedical Engineering (Discontinued) Synthesis, Characterization and Antitumor Activity of Novel Triazole/ Isoxazole Tagged Pyridine Hybrids
Letters in Organic Chemistry Purification and Characterization of Nitric Oxide Synthase from Bovine Kidney and Investigating Drug-Induced Toxicities of Some Antibiotics on the Enzyme Activity
Current Enzyme Inhibition The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Biological Interfacial Engineering for Metastatic Cancer Diagnosis and Intervention
Current Medicinal Chemistry Nanoplatforms for Promoting Osteogenesis in Ovariectomy-Induced Osteoporosis in the Experimental Model
Current Nanomedicine Antioxidant Food Supplements and Obesity-Related Inflammation
Current Medicinal Chemistry Curcumin: Structure-Activity Relationship Towards its Role as a Versatile Multi-Targeted Therapeutics
Mini-Reviews in Organic Chemistry 1,3,4-oxadiazole-2-thione Derivatives; Novel Approach for Anticancer and Tubulin Polymerization Inhibitory Activities
Anti-Cancer Agents in Medicinal Chemistry Screening for Genetic Mutations. A Review
Combinatorial Chemistry & High Throughput Screening Construction and Evaluation of Liraglutide Delivery System based on Milk Exosomes: A New Idea for Oral Peptide Delivery
Current Pharmaceutical Biotechnology Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections
Current Topics in Medicinal Chemistry Microbiology of the Human Intestinal Tract and Approaches for Its Dietary Modulation
Current Pharmaceutical Design Electrochemical Sensors for Hydroperoxides Based on Prussian Blue
Current Analytical Chemistry Postoperative Thoracic Epidural Anesthesia in Gastrointestinal Surgery: Outcomes, Quality of Life, and Current Controversies
Current Drug Therapy In Vitro Effects of Arylhydrocoumarin on Free Radicals and Oxidative Stress in Erythrocytes and Saccharomyces cerevisiae
Current Pharmaceutical Biotechnology Biodegradation Aspects of Carbendazim and Sulfosulfuron: Trends, Scope and Relevance
Current Medicinal Chemistry In Silico Classification and Prediction of VIP Derivatives as VPAC1/ VPAC2 Receptor Agonists/Antagonists
Combinatorial Chemistry & High Throughput Screening