Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene

Inada, Yasushi; Yanagawa, Hiroshi; Koh, Jun Sung; Sakai, Jun; Himei, Akio; Kinoshita, Yoko; Akabame, Kazuyo; Hiraoka, Yayoi; Sakai, Toshiaki

doi:10.1016/s0165-1781(03)00064-7

Cited by 71 publications

(49 citation statements)

References 33 publications

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“…The results of previous studies argued against a major role for the 5-HT2C receptor Cys23Ser polymorphism in PD (Fehr et al, 2000b;Inada et al, 2003). However, in our study, this polymorphism was significantly associated with PD in the total sample of patients with or without affective comorbidity (Maron et al, 2005b).…”

Section: -Ht Receptor Genescontrasting

confidence: 88%

“…However, the 5-HT-ergic genetic influence seems to be differently related to PD phenotypes and may be genderdependent. Furthermore, the results of several studies (Inada et al, 2003;Rothe et al, 2004a;Maron et al, 2005a) support the notion of Noyes et al (1986) that PD with agoraphobia is a more severe variant of PD with a stronger genetic component.…”

Section: -Ht Receptor Genesmentioning

confidence: 56%

“…Association of 5-HT1A -1019C-G with the presence of panic attacks was also observed in other psychiatric disorders, including major depression, bipolar disorder, and schizophrenia; however, this association was not present in patients with comorbid diagnosis of PD, probably due to the lower diagnostic reliability in the last group (Huang et al, 2004). Other data showed lack of association between PD phenotypes and several other 5-HTR1A receptor polymorphisms (Inada et al, 2003;Maron et al, 2005b). 5-HT1B receptor gene 861G-C polymorphism did not demonstrate any significant association in patients with PD (Fehr et al, 2000a;Maron et al, 2005a).…”

Section: -Ht Receptor Genesmentioning

confidence: 94%

“…Recently, Inada et al (2003) detected a significant association with 5-HT2A receptor silent 102T-C polymorphism in PD patients with pure phenotype and in particular with agoraphobia. Our study also showed a significant association with the 5-HT2A receptor 102T-C polymorphism in pure, but not in comorbid, PD (Maron et al, 2005b).…”

Section: -Ht Receptor Genesmentioning

confidence: 99%

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Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

106

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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Section: -Ht Receptor Genescontrasting

confidence: 88%

Section: -Ht Receptor Genesmentioning

confidence: 56%

Section: -Ht Receptor Genesmentioning

confidence: 94%

Section: -Ht Receptor Genesmentioning

confidence: 99%

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Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

106

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“…15 In association analyses, candidate genes including HTR 1A, 16 2A, 17,18 CCK, 19 ADORA2A, 20 MAOA 21 and COMT 22,23 have been investigated. Most of the association studies were, however, of small sample size (No200) and the results were controversial.…”

Section: Introductionmentioning

confidence: 99%

Replication of a genome-wide association study of panic disorder in a Japanese population

Otowa

Tanii

Sugaya³

et al. 2009

J Hum Genet

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Panic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks, subsequent worry and phobic avoidance. Although a number of association and linkage studies have been conducted, no gene has been identified as a susceptibility locus. We previously conducted a genome-wide association analysis of PD in 200 Japanese patients and the same number of controls, using a 500 K single nucleotide polymorphisms (SNPs) chip. In this study, we report a replication analysis of PD using the DigTag2 assay. The second stage sample consisted of 558 Japanese patients and 566 controls. Thirty-two markers were tested in a replication sample. As a result, no significant association was found after correction for multiple testing. However, the difference was observed at the nominal allele P-value o0.05 for two SNPs (rs6733840 and rs132617). We also conducted haplotype analyses of SNPs in the APOL3 and CLU genes. Our results failed to show any significant association with PD in these genes. Further studies on these variants with a larger sample size may be worth testing to confirm the results. Keywords: genome-wide association study (GWAS); Japanese population; panic disorder; replication; single nucleotide polymorphism (SNP) INTRODUCTIONPanic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks, subsequent worry and phobic avoidance. Life prevalence of PD is 1-3% and twice as many women as men suffer from the disorder. 1 The disorder frequently takes a chronic course, with many remissions and relapses. 2 Genetic epidemiological studies including family and twin studies have shown that genetic as well as environmental factors have an important role in the pathogeneses of PD. First-degree relatives of proband with PD have an approximately fivefold increased risk of PD. 3,4 Twin studies show that about 40% of the liability towards PD consists of heritable factors [5][6][7] However, the etiology of PD is currently unknown.

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Genetic Factors and Gene–Environment Interactions

Maron

Shlik

2014

The Wiley Handbook of Anxiety Disorders

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Previous genome-wide association studies (GWAS) have identified hundreds of genetic loci to be associated with body mass index (BMI) and risk of obesity. Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions. In this study, we examine gene-environment interactions in 362,496 unrelated participants with Caucasian ancestry from the UK Biobank resource. A total of 94 BMI-associated SNPs, selected from a previous GWAS on BMI, were used to construct weighted genetic scores for BMI (GS BMI). Linear regression modeling was used to estimate the effect of gene-environment interactions on BMI for 131 lifestyle factors related to: dietary habits, smoking and alcohol consumption, physical activity, socioeconomic status, mental health, sleeping patterns, as well as female-specific factors such as menopause and childbirth. In total, 15 lifestyle factors were observed to interact with GS BMI , of which alcohol intake frequency , usual walking pace, and Townsend deprivation index, a measure of socioeconomic status, were all highly significant (p = 1.45*10 −29 , p = 3.83*10 −26 , p = 4.66*10 −11 , respectively). Interestingly, the frequency of alcohol consumption, rather than the total weekly amount resulted in a significant interaction. The FTO locus was the strongest single locus interacting with any of the lifestyle factors. However, 13 significant interactions were also observed after omitting the FTO locus from the genetic score. Our analyses indicate that many lifestyle factors modify the genetic effects on BMI with some groups of individuals having more than double the effect of the genetic score. However, the underlying causal mechanisms of gene-environmental interactions are difficult to deduce from cross-sectional data alone and controlled experiments are required to fully characterise the causal factors. Author summary Genome-wide association studies (GWAS) have identified hundreds of genes as being associated with body mass index (BMI). How these genetic effects are modulated by lifestyle factors has not been extensively investigated previously. Here we utilise data from PLOS Genetics | https://doi.org/10.1371/journal.pgen.approximately 360,000 participants from the UK Biobank, aged 40-69 years old, to identify interactions between genetic and lifestyle factors in relation to BMI. We investigated 131 lifestyle factors, of which 15 influence the genetic effects on BMI. The most significant factors were those related to physical activity, alcohol consumption, and socioeconomic status. For example, the effect of a genetic score for BMI was almost twice as high in participants who reported never drinking alcohol compared to everyday drinkers. Similarly, the effect of the genetic score for BMI was 2.5 times higher in participants who reported having a slow walking pace compared to participants who reported having a brisk walking pace. Our results show that many lifestyle factors influence the genetic effects, which suggests that changing our lif...

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Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene

Cited by 71 publications

References 33 publications

Serotonin Function in Panic Disorder: Important, But Why?

Serotonin Function in Panic Disorder: Important, But Why?

Replication of a genome-wide association study of panic disorder in a Japanese population

Genetic Factors and Gene–Environment Interactions

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