Abstract
Genome-wide association (GWA) studies have shown that many different genetic variants cumulatively contribute to the risk of psychiatric disorders. It has also been demonstrated that various parent-of-origin effects (POE) may differentially influence the risk of these disorders. Together, these observations have provided important new possibilities to uncover the genetic underpinnings of such complex phenotypes. As POE so far have received little attention in neuropsychiatric disorders, there is still much progress to be made. Here, we mainly focus on the new and emerging role of POE in attention-deficit hyperactivity disorder (ADHD). We review the current evidence that POE play an imperative role in vulnerability to ADHD and related disorders. We also discuss how POE can be assessed using statistical genetics tools, expanding the resources of modern psychiatric genetics. We propose that better comprehension and inspection of POE may offer new insight into the molecular basis of ADHD and related phenotypes, as well as the potential for preventive and therapeutic interventions.
Highlights
Genome-wide association (GWA) studies have demonstrated that many different genetic variants cumulatively contribute to the risk of psychiatric disorders
Associations detected in case/control design may originate from genetic mechanisms other than those functioning in cases, but rather from their confounders, such as maternal genotype effects, imprinting and/or maternal-fetal interactions [5, 6]
This test assumes that a heterozygous group would exhibit increased phenotypic variability compared to a homozygous group, because it consists of two subgroups of reciprocal heterozygotes each with different phenotypic means. While this method has the benefit of analyzing parent-of-origin effects (POE) without trios, opening new potential of detecting POE in GWA data, it can lead to spurious conclusions when parental genetic effects are present
Summary
Genome-wide association (GWA) studies have demonstrated that many different genetic variants cumulatively contribute to the risk of psychiatric disorders. The GWA approach has been successful in schizophrenia, where over 108 susceptibility loci have been identified [1]. Despite this recent progress, little is yet known of the precise genes and molecular mechanisms involved, such as epigenetic risk factors transmitted across generations. Apart from the fact that ADHD is a multifactorial disorder and previous GWA studies have been underpowered, this may be due to a number of other factors, such as phenotypic heterogeneity, rare and unexplored variants, epistasis, gene × environment interaction as well as the presence of parent-of-origin effects (POE).
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