Many factors may explain the inconsistency between heritability estimated phenot

Question

Many factors may explain the inconsistency between heritability estimated phenotypically (e.g. based on pedigree) and heritability estimated from SNPs derived from GWAS (e.g. "missing heritability" problem), such as: genotype by genotype interactions, genotype by environment interactions, rare variants, and population structure. Propose an experiment or method of analysis that could go beyond the results obtained from a standard genome wide association study by accounting for one of these factors. Explain how your approach can find additional heritability that was originally missed by the typical GWAS approach.

Explanation / Answer

I would suggest that if we want to go beyond GWAS study, the "Genetic imaging" will be the best method as of today. Genetic imaging is about studying the anatomical and physiological association of certain genes expressed in the brain which have direct effect on the psychology and behaviour of individual with a particular trait or disease.

Method:-

1. Conduct fMRI (functional Magnetic Resonance Imaging) on the selected individuals under study.

2. Compare fMRI data of the same set of population to find any correlation between neuro functions and variations at the genetic level for a particular trait or disease.

This approach will help us to determin, in addition to original GWAS study, how differences in SNPs in individuals can have varying differences in the brain circuit make up and also the individual's intellectual performance.

Thus, additional heritability information can be obtained by such "neuro imaging phenotype" on the correlation between genes and brain function for particular disease or trait under study. This method is ideal for diseses such as Alzheimer's disease.

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