Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD

W. Guo, Jack Samuels, Ying Wang, H. Cao, M. Ritter, P. S. Nestadt, J. Krasnow, B. D. Greenberg, A. J. Fyer, J. T. McCracken, D. A. Geller, D. L. Murphy, J. A. Knowles, M. A. Grados, Mark A Riddle, S. A. Rasmussen, N. C. McLaughlin, E. L. Nurmi, K. D. Askland, B. A. CullenJ. Piacentini, D. L. Pauls, O. J. Bienvenu, S. E. Stewart, F. S. Goes, B. Maher, Ann E Pulver, D. Valle, M. Mattheisen, J. Qian, G. Nestadt, Y. Y. Shugart

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10−7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.

Original languageEnglish (US)
Pages (from-to)657-666
Number of pages10
JournalEuropean Neuropsychopharmacology
Issue number7
StatePublished - Jul 2017


  • ASD
  • GWAS
  • Heritability
  • Meta-analysis
  • OCD
  • Polygenic score

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


Dive into the research topics of 'Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD'. Together they form a unique fingerprint.

Cite this