Genetic study on small insertions and deletions in psoriasis revealed an important impact on complex human diseases

Abstract Genetic studies based on single nucleotide polymorphisms (SNPs) have provided valuable insights into the genetic architecture of complex diseases. However, a large fraction of heritability for most of these diseases remains unexplained, and the impact of small insertions and deletions (InDels) has been neglected.We performed a comprehensive screen on exome sequence data of 1,326 genes using the SOAP-PopIndel method for InDels in 32,043 Chinese Han individuals and identified 29 unreported InDels within 25 susceptibility genes associated with psoriasis. Specifically, we identified 12 common, 9 low-frequency and 8 rare InDels that explained approximately 1.29% of the heritability of psoriasis. Further analysesidentified KIAA0319, RELN,NCAPG, ABO, AADACL2 , LMAN1 , FLG , HERC5 , CCDC66 , LEKR1, AFF3, ABCG2, ANXA7, SYTL2,GIPR, METTL1, and FYCO1 as unreported genes for psoriasis. Additionally, identified InDels were associated with reported genes IFIH1, ERAP1, ERAP2, LNPEP, UBLCP1 and STAT3 , and unreported independent associations for exonic InDels were found within GJB2 and ZNF816A . Our study enriched the genetic basis and pathogenesis of psoriasis and highlighted the non-negligible impact of InDels on complex human diseases.