The major strength of sequencing is that it captures variants that have been previously uncharacterized by candidate gene and GWAS methods and thus may provide new insights into the genetic underpinnings of depression. Like all techniques, however, sequencing approaches face a number of challenges. For example, despite enormous reductions in the cost of sequencing, well-powered studies are still very expensive. Whole genome sequencing costs at least $1,000 US per genome, whereas exome sequencing costs several hundreds of dollars. Exome sequencing also assesses polymorphisms that by definition are rare and thus occur with much less frequently than common variants. To have sufficient statistical power to identify an association between these rare variants and depression, very large sample sizes, on the order of 10,000 or more cases, are needed. In addition, rare variant association methods are still largely under development.
