TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

Erhardt, Angelika; Czibere, Ludwig; Roeske, D.; Lucae, Susanne; Unschuld, Paul G.; Ripke, Stephan; Specht, Michael; Kohli, Martin; Kloiber, Stefan; Ising, Marcus; Heck, Angela; Pfister, Hildegard; Zimmermann, Petra; Lieb, Roselind; Pütz, Benno; Uhr, Manfred; Weber, Peter; Deussing, Jan M.; Gonik, Mariya; Bunck, Mirjam; Keßler, Melanie; Frank, Elisabeth; Hohoff, Christa; Domschke, Katharina; Krakowitzky, Petra; Maier, Wolfgang; Bandelow, Borwin; Jacob, Christian; Deckert, Jürgen; Schreiber, Stefan; Strohmaier, Jana; Nöthen, Markus M.; Cichon, Sven; Rietschel, Marcella; Bettecken, Thomas; Keck, Martin E.; Landgraf, Rainer; Müller‐Myhsok, Bertram; Holsboer, Florian; Binder, Elisabeth B.

doi:10.1038/mp.2010.41

Cited by 136 publications

(151 citation statements)

References 55 publications

(75 reference statements)

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“…An initial GWAS found association of a TMEM132D SNP (rs7309727) as well as a haplotype combining this and another SNP (rs11060369). Risk genotypes were associated with higher TMEM132D mRNA expression in human postmortem frontal cortex, results further supported by a mouse model in which high anxiety-related behavior was associated with a Tmem132d SNP and correlated with expression of Tmem132d mRNA in the anterior cingulate cortex (Erhardt et al, 2011). In a subsequent meta-analysis of eight independent case-control samples, genome-wide significant associations of rs7309727 and the haplotype of rs7309727-rs11060369 were reported when the analysis was restricted to European ancestry cases with primary PD (Erhardt et al, 2012).…”

Section: Common Genetic Variationsupporting

confidence: 50%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

358

243

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Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

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Section: Common Genetic Variationsupporting

confidence: 50%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

358

243

View full text Add to dashboard Cite

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“…Recent studies have shown a possible role of transmembrane gene 132D (TMEM132D) in the etiology of PD. 45,46 It might, therefore, be relevant to analyse these genes in future studies of PD.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene

et al. 2011

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Panic disorder (PD) is a mental disorder with recurrent panic attacks that occur spontaneously and are not associated to any particular object or situation. There is no consensus on what causes PD. However, it is recognized that PD is influenced by environmental factors, as well as genetic factors. Despite a significant hereditary component, genetic studies have only been modestly successful in identifying genes of importance for the development of PD. In this study, we conducted a genome-wide scan using microsatellite markers and PD patients and control individuals from the isolated population of the Faroe Islands. Subsequently, we conducted a fine mapping, which revealed the amiloride-sensitive cation channel 1 (ACCN1) located on chromosome 17q11.2-q12 as a potential candidate gene for PD. The further analyses of the ACCN1 gene using singlenucleotide polymorphisms (SNPs) revealed significant association with PD in an extended Faroese case-control sample. However, analyses of a larger independent Danish case-control sample yielded no substantial significant association. This suggests that the possible risk alleles associated in the isolated population are not those involved in the development of PD in a larger outbred population.

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“…The first data set originated from a panic disorder study 6 with a total of 299 468 SNPs, where 211 cases and 222 controls have been retained after standard quality control measures. Computing the difference of correlation coefficients across all pairs and choosing a P-value threshold of 1.0Â10 À5 resulted in a retention of 373 153 SNP pairs.…”

Section: Real Datamentioning

confidence: 99%

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

et al. 2010

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Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case-control studies and consists of a two-step process in which the difference in Pearson's correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair.

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TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

Cited by 136 publications

References 55 publications

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

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