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Eur Neuropsychopharmacol. 2017 Jul;27(7):657-666. doi: 10.1016/j.euroneuro.2017.03.011.

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

Author information

1
Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, USA.
2
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Elsevier Inc., Rockville, MD, USA.
4
Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
5
Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA.
6
New York State Psychiatric Institute, College of Physicians and Surgeons at Columbia University, New York, NY, USA.
7
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
8
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
9
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA.
10
Department of Psychiatry and Behavioral Sciences Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
11
Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
12
Institute of Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
13
Department of Biomedicine and Center for Integrated Sequencing (iSEQ), Aarhus University, Aarhus, Denmark; Harvard School of Public Health, Department of Biostatistics, Boston, MA, USA; Department of Genomic Mathematics, University of Bonn, Bonn, Germany.
14
Life Science Institutes, Fudan University, Shanghai, China.
15
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: gnestadt@jhmi.edu.
16
Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, USA. Electronic address: yin.yao@nih.gov.

Abstract

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.

KEYWORDS:

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

PMID:
28641744
DOI:
10.1016/j.euroneuro.2017.03.011
[Indexed for MEDLINE]

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