Volume 8 Issue 1 January, 2018
The foundation to human genetic studies was laid back in 1860s by the laws of inheritance proposed by Gregor Mendel. Psychiatric disorders are considered genetically complex with many genes being involved, probably acting in an additive manner. Several studies indicate that environmental factors modulate the genetic vulnerability toward the development of a mental illness. The high rate of findings not being replicated in other studies is attributable to factors such as sample size, differences in genomic structure, environmental exposures, and different diagnostic criteria used around the world.
Genetic Study Designs in Psychiatry:
- Epidemiological Studies:
A. Family Studies:
These studies look for a familial aggregation of the disorder, which means that the illness should occur at a higher rate in family members of affected people than the control population, this can be either due to shared genes or shared environment.
B. Twin Studies:
Twins can be either Monozygotic (MZ) share 100% of genes, Dizygotic (DZ) share around 50% of genes. If a disorder is only due to genes then concordance rates will be higher in MZ and will be 100%
C. Adoption Studies:
These clarify nature Vs nurture debate of an illness. These are either those who share the same genes, but different environment or those who share the same environment but different genes - Molecular Genetic Studies:
A position on a chromosome is termed a locus refers to a gene or segment of DNA with no known function. DNA sequences that differ at the same locus are termed allelic variants. Polymorphism in the human genome permits gene mapping, and disease gene identification.
A. Linkage Studies: These studies try to establish a link between the DNA polymorphic markers and their heritability among the affected members in the family. Linkage studies assume that these markers are closest to the disease loci. Examples of these markers are: Restriction fragment length polymorphisms (RFLP), short tandem repeat markers, microsatellites DNA sequences and more recently single nucleotide polymorphisms (SNPs).
B. Association Studies: These are more commonly used in psychiatric disorders; they are of two types, case-control design – where the allele frequencies are compared between a group of unrelated affected individuals and a matched control sample. Family based design – mother, father and an affected offspring trio are studied. Association studies focus on testing one or a few markers in candidate genes chosen on the basis of their hypothesized function in relation to a given disease.
Epigenetics:
This refers to the changes in the genetic material like methylation of DNA and modifications of chromatin, such as methylation and acetylation of the histones, the DNA’s packaging material which lead to phenotypic changes without altering the DNA sequences. They are acquired during the life of the person. In complex disorders like psychiatric disorders understanding the interplay between epigenetics and genetics is very important.
What does the future behold?
The understanding that we have from the work so far is that, it is not rare mutations in one or more genes but multiple susceptibility alleles that lead to common variants which are responsible for psychiatric disorders, and this is the reason why there are high rates co-morbidity and diagnostic uncertainties. This understanding has paved way to new approaches to the design, analysis and interpretation of psychiatric genetic studies. Some of these are the study of candidate genes and study of endo-phenotypes which are quantifiable phenotypes associated with psychiatric illness.
Dr. Preeti Reddy, Clinical Post Doctoral Fellow, NIMHANS, Bengaluru
