The landscape of copy number variations in Finnish families with autism spectrum disorders

Research output: Contribution to journalArticle


  • Chakravarthi Kanduri
  • Katri Kantojärvi
  • Paula M. Salo
  • Raija Vanhala
  • Gemma Buck
  • Christine Blancher
  • Harri Lähdesmäki

  • Irma Järvelä

Research units

  • University of Helsinki
  • Wellcome Trust Centre for Human Genetics


Rare de novo and inherited copy number variations (CNVs) have been implicated in autism spectrum disorder (ASD) risk. However, the genetic underpinnings of ASD remain unknown in more than 80% of cases. Therefore, identification of novel candidate genes and corroboration of known candidate genes may broaden the horizons of determining genetic risk alleles, and subsequent development of diagnostic testing. Here, using genotyping arrays, we characterized the genetic architecture of rare CNVs ( 1 Mb) CNVs and rare, exonic CNVs. The exonic rare de novo CNV rate (~ 22.5%) seemed higher compared to previous reports. We identified several CNVs in well-known ASD regions including GSTM1-5, DISC1, FHIT, RBFOX1, CHRNA7, 15q11.2, 15q13.2-q13.3, 17q12, and 22q11.21. Additionally, several novel candidate genes (BDKRB1, BDKRB2, AP2M1, SPTA1, PTH1R, CYP2E1, PLCD3, F2RL1, UQCRC2, LILRB3, RPS9, and COL11A2) were identified through gene prioritization. The majority of these genes belong to neuroactive ligand-receptor interaction pathways, and calcium signaling pathways, thus suggesting that a subset of these novel candidate genes may contribute to ASD risk. Furthermore, several metabolic pathways like caffeine metabolism, drug metabolism, retinol metabolism, and calcium-signaling pathway were found to be affected by the rare exonic ASD CNVs. Additionally, biological processes such as bradykinin receptor activity, endoderm formation and development, and oxidoreductase activity were enriched among the rare exonic ASD CNVs. Overall, our findings may add data about new genes and pathways that contribute to the genetic architecture of ASD.


Original languageEnglish
Pages (from-to)9-16
Number of pages8
Issue number1
Publication statusPublished - 1 Jan 2016
MoE publication typeA1 Journal article-refereed

    Research areas

  • Autism spectrum disorders, Copy number variations, Finnish population, Genome wide SNP arrays

ID: 1536117