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

W. Guo; J. F. Samuels; Y. 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; M. A. Riddle; S. A. Rasmussen; N. C. McLaughlin; E. L. Nurmi; K. D. Askland; B. A. Cullen; J. Piacentini; D. L. Pauls; O. J. Bienvenu; S. E. Stewart; F. S. Goes; B. Maher; A. E. Pulver; D. Valle; M. Mattheisen; J. Qian; G. Nestadt; Y. Y. Shugart

doi:10.1016/j.euroneuro.2017.03.011

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

W. Guo, J. F. Samuels, Y. 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, M. 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, A. E. Pulver, D. Valle, M. Mattheisen, J. Qian, G. Nestadt, Y. Y. Shugart

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19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	657-666
Number of pages	10
Journal	European Neuropsychopharmacology
Volume	27
Issue number	7
DOIs	https://doi.org/10.1016/j.euroneuro.2017.03.011
State	Published - Jul 2017

Keywords

ASD
GWAS
Heritability
Meta-analysis
OCD
Polygenic score

ASJC Scopus subject areas

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

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Guo, W., Samuels, J. F., Wang, Y., Cao, H., Ritter, M., Nestadt, P. S., Krasnow, J., Greenberg, B. D., Fyer, A. J., McCracken, J. T., Geller, D. A., Murphy, D. L., Knowles, J. A., Grados, M. A., Riddle, M. A., Rasmussen, S. A., McLaughlin, N. C., Nurmi, E. L., Askland, K. D., ... Shugart, Y. Y. (2017). Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD. European Neuropsychopharmacology, 27(7), 657-666. https://doi.org/10.1016/j.euroneuro.2017.03.011

Guo, W, Samuels, JF, Wang, Y, Cao, H, Ritter, M, Nestadt, PS, Krasnow, J, Greenberg, BD, Fyer, AJ, McCracken, JT, Geller, DA, Murphy, DL, Knowles, JA, Grados, MA, Riddle, MA, Rasmussen, SA, McLaughlin, NC, Nurmi, EL, Askland, KD, Cullen, BA, Piacentini, J, Pauls, DL, Bienvenu, OJ, Stewart, SE, Goes, FS , Maher, B, Pulver, AE, Valle, D, Mattheisen, M, Qian, J, Nestadt, G & Shugart, YY 2017, 'Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD', European Neuropsychopharmacology, vol. 27, no. 7, pp. 657-666. https://doi.org/10.1016/j.euroneuro.2017.03.011

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title = "Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD",

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",

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

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year = "2017",

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doi = "10.1016/j.euroneuro.2017.03.011",

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AU - Guo, W.

AU - Samuels, J. F.

AU - Wang, Y.

AU - Cao, H.

AU - Ritter, M.

AU - Nestadt, P. S.

AU - Krasnow, J.

AU - Greenberg, B. D.

AU - Fyer, A. J.

AU - McCracken, J. T.

AU - Geller, D. A.

AU - Murphy, D. L.

AU - Knowles, J. A.

AU - Grados, M. A.

AU - Riddle, M. A.

AU - Rasmussen, S. A.

AU - McLaughlin, N. C.

AU - Nurmi, E. L.

AU - Askland, K. D.

AU - Cullen, B. A.

AU - Piacentini, J.

AU - Pauls, D. L.

AU - Bienvenu, O. J.

AU - Stewart, S. E.

AU - Goes, F. S.

AU - Maher, B.

AU - Pulver, A. E.

AU - Valle, D.

AU - Mattheisen, M.

AU - Qian, J.

AU - Nestadt, G.

AU - Shugart, Y. Y.

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

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KW - Heritability

KW - Meta-analysis

KW - OCD

KW - Polygenic score

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

Abstract

Keywords

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