Ulrich Bodenhofer, Sepp Hochreiter,
"Making Sense of Very Rare and Private Single-Nucleotide Variants"
: Proceedings MAQC Society Second Annual Meeting, 2018
Original Titel:
Making Sense of Very Rare and Private Single-Nucleotide Variants
Sprache des Titels:
Englisch
Original Buchtitel:
Proceedings MAQC Society Second Annual Meeting
Original Kurzfassung:
High-throughput sequencing technologies have facilitated the identification of large numbers of singlenucleotide
variations (SNVs), many of which have already been proven to be associated with diseases or
other complex traits. Several large sequencing studies, such as, the 1000 Genomes Project, the UK10K
project, or the NHLBI-Exome Sequencing Project, have consistently reported a large proportion of
private SNVs, that is, variants that are unique to a family or even a single individual. The role of private
SNVs in diseases is poorly understood, largely due to the fact that it is statistically very challenging to
consider private SNVs in association testing. While it is generally impossible to make use of private
SNVs in single-marker tests or in correlation-based tests like the popular SNP-set (Sequence) Kernel
Association Test (SKAT), also burden tests are facing serious statistical issues. We have proposed the Position-Dependent Kernel Association Test (PODKAT), which is designed for
detecting associations of very rare and private SNVs with the trait under consideration even if the
burden scores are not correlated with the trait. The test assumes that, the closer two SNVs are on the
genome, the more likely they have similar effects on the trait under consideration. This assumption is
fulfilled as long as deleterious, neutral, and protective variants are grouped sufficiently well along the
genome.