**3.6 Association studies**

Associations indicate that the presence of an allele confers risk for disease within a specific environment. Allele association helps to identify whether the frequency of an allele is considerably increased or decreased in a particular disease. The difference between association studies and genetic linkage is that association studies compare a population of affected individuals with control population whereas, the latter is demonstrable only in families or siblings.

Therefore, Association studies involve candidate gene approach, a gene mapping approach that tests whether one allele of a gene appears more frequently in patients with disease than in subjects without the disease. Candidate genes are selected based on their reasonable role in disease process such as producing a protein that is important in disease pathogenesis.

Linkage disequilibrium is a term used when the same marker allele is linked with disease in multiple families. Frequency of allele at a given locus is compared between patients with disease and healthy subjects to test this association. Biologic link between the disease and an allele cannot be confirmed through association. Association might result due to few environmental factors causing both the marker and the disease to rise in the population, or due to a difference in the racial or ethnic makeup of the cases and controls, or from chance alone [29]. True linkage disequilibrium refers to a situation when marker and disease allele are placed close to each other on chromosomes and the chances of disease are more.

On the whole, this population-based approach compares marker allele frequencies between affected and unaffected individuals, using a standard case–control design. When a positive association is found, few interpretations are made: [30].


Numerous case control studies are reported in which genotype frequencies of an inherited DNA variant for a group of periodontitis cases are statistically compared to periodontally healthy control subjects. If the genotype frequencies vary so much that the results are very unlikely to occur by coincidence, it is assumed that the genotype is more common in cases than controls and is associated with high disease risk.

### *3.6.1 Advantages*

Association studies are beneficial for discovery of inherited genetic variation important for a wide range of complex diseases including diabetes, cardiovascular diseases, metabolic disorders, obesity and mental illness.
