Association (genetics)

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In genetics, association describes the common occurrence or occurrence of two genetic features with a frequency that is higher (i.e. more frequent) than would be expected by chance. A distinction can be made between a phenotypic association, in which a phenotypic characteristic (such as a hereditary disease) occurs more frequently than by chance together with a genetic characteristic, such as an allele of a specific gene , and an allelic association, in which a specific allele occurs at a gene locus , the occurrence of another allele at a second gene locus is more or less frequent than expected. A closely related term in genetics is that of gene coupling . Both have in common that the respective relationship deviates from a random distribution according to Mendel's rule of independence (“third Mendel's law”). It can be said that a genetic linkage is based on a connection between two gene loci, whereas the association is based on the connection between two alleles (or: an allele and a trait). The two are not mutually exclusive: If a coupling is found, an association can often also exist, and vice versa.

Association analysis and linkage analysis: genetic epidemiology

In an association analysis, the frequency of a certain allele (or a characteristic) is statistically compared with the occurrence of another allele, which can occur less or more frequently than expected in the carriers of the characteristic. There can, but need not, be a connection between the allele and the characteristic; they can also be associated with one another through indirect effects.

In contrast, the linkage analysis looks directly at the relationship between the trait and the allelic expression at certain gene loci by examining the inheritance . If these are inherited more often than would be expected by chance, they are linked, mostly because they are more or less closely adjacent on the same chromosome . The closer they are to each other, the closer the coupling, since they are less frequently redistributed during the crossing-over during genetic recombination . In the association analysis, however, inheritance is not taken into account at all. Two collectives, say two groups of patients, are simply examined to see how often a certain allele occurs in them. If an allele is more common in a diseased group than in a healthy group, there is an association between the allele and the disease. If, in general, two alleles occur together in one of the groups more frequently than would be expected by chance, there is an association between them.

Coupling imbalance

The association of an allele with a characteristic can be based on the presence of a gene linkage. It often happens that association analyzes determine a statistical connection between an allele and a trait, although the allele genetically has absolutely nothing to do with the trait and its expression. This is the case when the (examined, and therefore known) allele is genetically linked to a (not examined, and possibly as yet unknown) second allele that is actually involved in the expression of the characteristic. Due to the coupling, both occur together more often than expected. This means that the trait occurs more frequently together with the first allele, although there is only an indirect connection here. In such a case, the term linkage imbalance is used. However, the corresponding term from the English technical language, "linkage disequilibrium", is simply left untranslated in German-language publications. It should be noted that geneticists are often careless in their use of language. It has become common to speak of linkage disequilibrium even if the connection is not due to the linkage of genes , but is purely statistical (this has historical reasons, as the linkage could already be researched by logging the inheritance when it was not routinely possible was to sequence genes too). The English term linkage disequilibrium and the term genetic association are largely synonymous and synonymous.

GWAS

Since, in the age of genomics, even longer genomes can be routinely examined quickly and inexpensively, association analyzes have been carried out on a large scale and routinely, with the hope that through the throughput of very large amounts of data, by chance, interesting relationships, e.g. between a certain allele and a disease, even if little or nothing is known about the gene in question, i.e. no connection could be derived from the mechanism. It is hoped that this will lead to genetic connections that have not yet been found by direct examination. The research direction is called genome-wide association studies , abbreviated GWAS. Statistically significant associations are collected in a special database, the Genetic Association Database of the National Institutes of Health , so that they are also available to other scientists as a basis for their research.

Web links

Individual evidence

  1. ↑ association. In: Robert C. King, William D. Stansfield, Pamela K. Mulligan: A Dictionary of Genetics. 7th edition. Oxford University Press, 2006, ISBN 0-19-530762-3 .
  2. ↑ a b Detlev Ganten, Klaus Ruckpaul: Fundamentals of molecular medicine. 2nd Edition. Springer-Verlag, 2013, ISBN 978-3-662-07588-3 , p. 103.
  3. ↑ J. Graw: Genetics. Springer, 2010, ISBN 978-3-642-04998-9 , p. 625.
  4. ^ A b Andreas Ziegler: Genetic Epidemiology - Present and Future. In: Deutsches Ärzteblatt. 99, 36, 2002, pp. 2342-2346.
  5. ↑ Montgomery Slatkin: Linkage disequilibrium - understanding the evolutionary past and mapping the medical future. In: Nature Reviews Genetics. 9, 2008, pp. 477-485. doi: 10.1038 / nrg2361
  6. ^ Genetic Association Database