No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci

Most genetic studies assume that the function of a genetic variant is independent of the parent from which it is inherited, but this is not always true. The best known example of parent-of-origin effects arises with respect to alleles at imprinted loci. In classical imprinting, characteristically, e...

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Main Authors:	Escott-Price, Valentina, Kirov, George, Rees, Elliott, Isles, Anthony R., Owen, Michael J., O’Donovan, Michael C.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669201/

id	pubmed-4669201
recordtype	oai_dc
spelling	pubmed-46692012015-12-10 No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci Escott-Price, Valentina Kirov, George Rees, Elliott Isles, Anthony R. Owen, Michael J. O’Donovan, Michael C. Research Article Most genetic studies assume that the function of a genetic variant is independent of the parent from which it is inherited, but this is not always true. The best known example of parent-of-origin effects arises with respect to alleles at imprinted loci. In classical imprinting, characteristically, either the maternal or paternal copy is expressed, but not both. Only alleles present in one of the parental copies of the gene, the expressed copy, is likely to contribute to disease. It has been postulated that imprinting is important in central nervous system development, and that consequently, imprinted loci may be involved in schizophrenia. If this is true, allowing for parent-of-origin effects might be important in genetic studies of schizophrenia. Here, we use genome-wide association data from one of the world’s largest samples (N = 695) of parent schizophrenia-offspring trios to test for parent-of-origin effects. To maximise power, we restricted our analyses to test two main hypotheses. If imprinting plays a disproportionate role in schizophrenia susceptibility, we postulated a) that alleles showing robust evidence for association to schizophrenia from previous genome-wide association studies should be enriched for parent-of-origin effects and b) that genes at loci imprinted in humans or mice should be enriched both for genome-wide significant associations, and in our sample, for parent-of-origin effects. Neither prediction was supported in the present study. We have shown, that it is unlikely that parent-of-origin effects or imprinting play particularly important roles in schizophrenia, although our findings do not exclude such effects at specific loci nor do they exclude such effects among rare alleles. Public Library of Science 2015-12-03 /pmc/articles/PMC4669201/ /pubmed/26633303 http://dx.doi.org/10.1371/journal.pone.0144172 Text en © 2015 Escott-Price et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Escott-Price, Valentina Kirov, George Rees, Elliott Isles, Anthony R. Owen, Michael J. O’Donovan, Michael C.
spellingShingle	Escott-Price, Valentina Kirov, George Rees, Elliott Isles, Anthony R. Owen, Michael J. O’Donovan, Michael C. No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
author_facet	Escott-Price, Valentina Kirov, George Rees, Elliott Isles, Anthony R. Owen, Michael J. O’Donovan, Michael C.
author_sort	Escott-Price, Valentina
title	No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
title_short	No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
title_full	No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
title_fullStr	No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
title_full_unstemmed	No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci
title_sort	no evidence for enrichment in schizophrenia for common allelic associations at imprinted loci
description	Most genetic studies assume that the function of a genetic variant is independent of the parent from which it is inherited, but this is not always true. The best known example of parent-of-origin effects arises with respect to alleles at imprinted loci. In classical imprinting, characteristically, either the maternal or paternal copy is expressed, but not both. Only alleles present in one of the parental copies of the gene, the expressed copy, is likely to contribute to disease. It has been postulated that imprinting is important in central nervous system development, and that consequently, imprinted loci may be involved in schizophrenia. If this is true, allowing for parent-of-origin effects might be important in genetic studies of schizophrenia. Here, we use genome-wide association data from one of the world’s largest samples (N = 695) of parent schizophrenia-offspring trios to test for parent-of-origin effects. To maximise power, we restricted our analyses to test two main hypotheses. If imprinting plays a disproportionate role in schizophrenia susceptibility, we postulated a) that alleles showing robust evidence for association to schizophrenia from previous genome-wide association studies should be enriched for parent-of-origin effects and b) that genes at loci imprinted in humans or mice should be enriched both for genome-wide significant associations, and in our sample, for parent-of-origin effects. Neither prediction was supported in the present study. We have shown, that it is unlikely that parent-of-origin effects or imprinting play particularly important roles in schizophrenia, although our findings do not exclude such effects at specific loci nor do they exclude such effects among rare alleles.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669201/
_version_	1613509395976552448

No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci

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