Genomics in the AWS Cloud

CHAPTER 11Variants and Applications

In this chapter, we look at some applications of the analysis of genomes. We first investigate polygenic risk scores, which capture the additive effects of thousands of variants to influence our complex traits. We then extend our study to metagenomics and explore how metagenomics can be applied to human samples.

Polygenic Risk Scores

We know from twins studies that certain traits and health conditions are highly hereditary. Studies of identical and fraternal twins suggest, for example, that up to 80 percent of height variation is genetic. However, as the determination of height involves many variants along the genome, up to recently only 5 percent of height heritability could be explained. This paradox is referred to as the missing heritability problem. Rare diseases are often caused by a defective gene; in contrast, many traits and most common diseases are caused by hundreds or thousands of genetic variations.

Genome-wide Association Studies

Finding these causal variants requires undertaking large studies called genome-wide association studies (GWASs), which look for associations between traits and genetic variants, in other terms, associations between phenotype and genotype, in a population. Although GWASs can study copy number variants or other sequence variations, most GWASs focus on single nucleotide variants (SNVs). GWASs were performed from microarrays in the past and are currently commonly conducted from WXS or WGS. There are about ...