Genetic and epigenetic analyses of panic disorder in the post-GWAS era

Abstract

Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.

Examining individual differences in personality trait changes after negative life events

“…However, very small effects are not specific for research on personality traits. For example, individual genes can only account for a very small proportion of variance and individual differences in these effects based on epigenetic variants may be even harder to detect (Holland et al, 2016; Morimoto et al, 2020; Mott, 2022; Sullivan, 2010). Thus, learning from this area of research, we probably need large-scale, multi-lab, multi-national studies with many more participants than are customary in personality change research to better understand the implications of life events (Bleidorn et al, 2020).…”

Examining Individual Differences in Personality Trait Changes After Negative Life Events

“…However, very small effects are not specific for research on personality traits. For example, individual genes can only account for a very small proportion of variance and individual differences in these effects based on epigenetic variants may be even harder to detect (Holland et al, 2016;Morimoto et al, 2020;Mott, 2022;Sullivan, 2010). Thus, learning from this area of research, we probably need largescale, multi-lab, multi-national studies with several many more participants than are customary in personality change research to better understand the implications of life events (Bleidorn et al, 2020).…”

Genetic contributions to anxiety disorders: where we are and where we are heading

“…In addition, whole exome sequencing is increasingly used to investigate rare variants. However, to date no rare variant associations have been found for anxiety disorders (Gregersen et al, 2016; Kawamura et al, 2011; Morimoto et al, 2020) (See list of preliminary findings in Table 2). This is not surprising as GWAS in anxiety disorders have already shown that more than 100 000 individuals are needed for stable results on common variants and previous studies on rare variants have been far from this sample size.…”