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Genome-Wide Association Study: SNPs to Disease Associations

BY: Chandra Kala | Category: Others | Submitted: 2012-11-13 02:35:51
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Article Summary: "Genome-Wide Association Study (GWAS) is a high throughput study which involves analysis of genetic variants between different study groups to find associations between Single Nucleotide Polymorphisms (SNPs) to Phenotype or trait. GWA study is mainly associated with researches which focus on finding SNPs associations with phenot.."


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Genome-Wide Association Study (GWAS) is a high throughput study which involves analysis of genetic variants between different study groups to find associations between Single Nucleotide Polymorphisms (SNPs) to Phenotype or trait. GWA study is mainly associated with researches which focus on finding SNPs associations with phenotypes such as Diseases, Drug effects, and understanding the involvement of Genes in complex diseases.

GWA studies compare the genetic material / DNA between two groups called case and control. The control group will be generally the healthier individuals and case group will consists of disease or drug administrated subjects. The DNA has four nucleotides as Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). In the genome, instead of A if T, C, or G nucleotides are present, then it is Single nucleotide mutation (point mutation) and depending on the frequencies, the mutation is termed as Single nucleotide polymorphism (SNP) if it occurs in more than 1% of the population. Each nucleotide changed from the original sequence becomes the allelic form of the wild type. The wild type allele is the nucleotide base that is occurring in majority of the individuals. Each human consists of million SNPs differing from each other. Hence in GWAS, by comparing case and control, identifies few variants SNPs occurring in higher frequencies in either case or control. The SNPs that occurs in high frequencies in case are considered important as they are associated with either onset of Disease or drug effects, etc. The SNPs with higher risk of disease development are referred as genetic markers or risk allele and are further used in diagnosis purposes and in preventive medicines.

GWAS design consists of preparation of DNA samples from two groups (Case Vs Control) and hybridization of the DNA samples on to DNA chips. The bound DNA is amplified and further sequenced. The sequenced DNA is then assembled and the variations are counted. Statistical evaluations methods are applied to retain the variations that are statistically acceptable. The SNPs are reported with ODDS ratio and P-value. The Odds ratio is the ratio of occurrence of single SNPs between the case group and control group. The Odds ratio of greater than 1 informs the occurrence of those SNPs in case group is higher and Odds ration of lesser than 1 informs that the control group has higher frequency of the SNP. In the GWAS design, several other variables such as Gender, Age, and Geography / Ethnicity of the study population play a critical role in the associations of SNPs to phenotypes.

Research on GWAS is increasing day by day and there are thousands of research papers available. GWAS studies are carried on several diseases such as Cardiovascular diseases, Breast Cancer, Atherosclerosis, Both Type 1 and 2 Diabetes, Ovarian Cancer, Alzheimer's disease etc. There are several genetic variants now considered as genetic markers which inform that the presence of them has increased risk of acquiring diseases to the individuals. Food and Drug Administration (FDA) has approved many such genetic markers to be used in preventive diagnosis. Several Clinics are now routinely doing these risk alleles diagnosis either for treating the diseases or in knowing the risk of occurrence of any diseases in near future for the subject/ individual.


The successful application of GWAS is in the area of Clinical Research, which will help in diagnostic development and drug actions. The identification of associated risk SNPs with diseases helps to give accurate medicines for treating the diseases and avoiding the complications of side effects of drugs. GWAS will help to understand the Pharmacodynamics and Pharmacokinetics of Drugs. The associations of SNPs with phenotypes of Drug metabolism and Drug effects, has a great potential since it helps to avoid unnecessary usage of Drugs. The individuals with variant SNPs that show good response for a drug in lower does, then to such individual's lower doses of drug can be administrated. Similarly when the individuals has SNPs that are non response for a drug, then an alternative drug can be administrated thereby decreasing the side effects of the drug which has no effect on the individual. Considering the potential advantages of GWAS in the field of Pharmacology and human diseases, it has tremendous applications in the field of Personal Medicine in near future.

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