title: No Evidence for Enrichment in Schizophrenia for Common Allelic Associations at Imprinted Loci.
abstract: 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.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Valentina
authors.initials: V
authors.lastname: Escott-Price
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Elliott
authors.initials: E
authors.lastname: Rees
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Isles
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, Cardiff, United Kingdom.
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D000483:Alleles; D000818:Animals; D030541:Databases, Genetic; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000235:genetics*