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In genetic epidemiology, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS) or common-variant association study (CVAS), is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. GWASs typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major diseases. These studies normally compare the DNA of two groups of participants: people with the disease (cases) and similar people without (controls). This approach is known as phenotype-first, in which the participants are classified first by their clinical manifestation(s), as opposed to genotype-first. Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If one type of the variant (one allele) is more frequent in people with the disease, the SNP is said to be ''associated'' with the disease. The associated SNPs are then considered to mark a region of the human genome that influences the risk of disease. In contrast to methods that specifically test one or a few genetic regions, the GWA studies investigate the entire genome. The approach is therefore said to be ''non-candidate-driven'' in contrast to ''gene-specific candidate-driven studies''. GWA studies identify SNPs and other variants in DNA associated with a disease, but that cannot on their own specify which genes are causal.〔(【引用サイトリンク】title=Genome-Wide Association Studies )〕 The first successful GWAS was published in 2005. It investigated patients with age-related macular degeneration and found two SNPs with significantly altered allele frequency compared to healthy controls. , hundreds or thousands of individuals are tested, over 1,200 human GWA studies have examined over 200 diseases and traits, and almost 4,000 SNP associations have been found. Several GWA studies have received criticism for omitting important quality control steps, rendering the findings invalid, but modern publications address these issues. However, the methodology itself still has opponents. ==Background== Any two human genomes differ in millions of different ways. There are small variations in the individual nucleotides of the genomes (SNPs) as well as many larger variations, such as deletions, insertions and copy number variations. Any of these may cause alterations in an individual's traits, or phenotype, which can be anything from disease risk to physical properties such as height. Around the year 2000, prior to the introduction of GWA studies, the primary method of investigation was through inheritance studies of genetic linkage in families. This approach had proven highly useful towards single gene disorders.〔(【引用サイトリンク】 Online Mendelian Inheritance in Man )〕 However, for common and complex diseases the results of genetic linkage studies proved hard to reproduce.〔 A suggested alternative to linkage studies was the genetic association study. This study type asks if the allele of a genetic variant is found more often than expected in individuals with the phenotype of interest (e.g. with the disease being studied). Early calculations on statistical power indicated that this approach could be better than linkage studies at detecting weak genetic effects. In addition to the conceptual framework several additional factors enabled the GWA studies. One was the advent of biobanks, which are repositories of human genetic material that greatly reduced the cost and difficulty of collecting sufficient numbers of biological specimens for study. Another was the International HapMap Project, which, from 2003 identified a majority of the common SNPs interrogated in a GWA study. The haploblock structure identified by HapMap project also allowed the focus on the subset of SNPs that would describe most of the variation. Also the development of the methods to genotype all these SNPs using genotyping arrays was an important prerequisite. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Genome-wide association study」の詳細全文を読む スポンサード リンク
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