“What’s the Answer” Thread
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BioStar Question of the Week:
What’s the difference between GWAS and genome wide linkage studies?
I don’t understand the difference between a GWA (genome wide association study) and a GWLS (genome wide linkage study). I’m a computer scientist having to brush up biology!
The accepted, and well detailed answer is from David Quigley. Of course, if you are deep into GWAS and similar studies the answer is obvious , but for those who are new to the field or interesting in it…
…Linkage studies are performed when you have pedigrees of related individals and a phenotype (such as breast cancer) that is present in some but not all of the family members. These individuals could be humans or animals; linkage in humans is studied using existing families, so no breeding is involved. For each locus, you tabulate cases where parents and children who do or don’t show the phenotype also have the same allele. Linkage studies are the most powerful approach when studying highly penetrant phenotypes, which means that if you have the allele you have a strong probability of exhibiting the phenotype. They can identiy rare alleles that are present in small numbers of families, usualy due to a founder mutation. Linkage is how you find an allele such as the mutations in BRCA1 associated with breast cancer.
Association studies are used when you don’t have pedigrees; here the statistical test is a logistic regression or a related test for trends. They work when the phenotype has much lower penetrance; they are in fact more powerful than linkage analysis in those cases, provided you have enough informative cases and matched controls. Association studies are how you find common, low penetrance alleles such as the variations in FGFR2 that confer small increases in breast cancer susceptibility…