Genotype-first approach

The genotype-first approach is a type of strategy used in genetic epidemiological studies to associate specific genotypes to apparent clinical phenotypes of a complex disease or trait.

As opposed to “phenotype-first”, the traditional strategy that has been guiding genome-wide association studies (GWAS) so far, this approach characterizes individuals first by a statistically common genotype based on molecular tests prior to clinical phenotypic classification.

This method of grouping leads to patient evaluations based on a shared genetic etiology for the observed phenotypes, regardless of their suspected diagnosis.

Thus, this approach can prevent initial phenotypic bias and allow for identification of genes that pose a significant contribution to the disease etiology.

However, the implications from these studies can have valuable clinical applications, including improved diagnosis, counselling, and support groups for individuals with the same genetic etiology.

[1] Initially the idea of identifying the genotype of individuals and subsequently their associated phenotype(s) was first used in early cytogenetic studies.

These features limit the ability of both research and clinical studies to designate causal genes or variants to the observed phenotypes and to classify disorders.

In addition, researchers also discovered novel splice variants in the LPA gene that reduce apolipoprotein A levels and offer a protective phenotype against cardiovascular disease.