With the development of next-generation sequencing technology, de novo
variants (DNVs) with deleterious effects can be identified and investigated
for their effects on birth defects such as congenital heart disease (CHD).
However, statistical power is still limited for such studies because of the
small sample size due to the high cost of recruiting and sequencing samples
and the low occurrence of DNVs. DNV analysis is further complicated by
genetic heterogeneity across diseased individuals. Therefore, it is
critical to jointly analyze DNVs with other types of genomic/biological
information to improve statistical power to identify genes associated with
birth defects. In this review, we discuss the general workflow, recent
developments in statistical methods, and future directions for DNV
analysis.
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