Genome‐wide association study of theta band event‐related oscillations identifies serotonin receptor gene <i>HTR7</i> influencing risk of alcohol dependence

Zlojutro, Mark; Manz, Niklas; Rangaswamy, Madhavi; Xuei, Xiaoling; Flury-Wetherill, Leah; Koller, Daniel L.; Bierut, Laura J.; Goate, Alison M.; Hesselbrock, Victor; Kuperman, Samuel; Nürnberger, John I.; Rice, John P.; Schuckit, Marc A.; Foroud, Tatiana; Edenberg, Howard J.; Porjesz, Bernice; Almasy, Laura

doi:10.1002/ajmg.b.31136

Cited by 71 publications

(74 citation statements)

References 110 publications

(137 reference statements)

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“…Genetic association studies (Bierut et al, 2007;Edenberg et al, 2010;Zlojutro et al, 2011), eg, Collaborative Study on the Genetics of Alcoholism, have reported that a wide number of candidate genes contribute to the risk for alcoholism and other substance use disorders.…”

Section: Introductionmentioning

confidence: 99%

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Cao

Hudziak

2013

Neuropsychopharmacol

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A number of studies have reported associations between the serotonin transporter gene (SLC6A4) and alcohol, heroin, cocaine, or methamphetamine abuse. Other studies have yielded contrary results. There are a number of reasons for non-replication, including inadequate statistical power, population stratification, and poor phenotype definition. This study was to test the association using a meta-analytic approach across a variety of racial and ethnic populations. Using the genotype data of 55 studies (7999 cases, 8264 controls, and 676 families or parent-offspring trios) published in the past 15 years, we have conducted comprehensive meta-analyses to examine the associations of the 5-HTTLPR and STin2 polymorphisms with substance use disorder. The meta-analyses support the associations of 5-HTTLPR with alcohol, heroin, cocaine, and methamphetamine dependence and abuse (eg, the smallest P-values were 0.0058 with odds ratio (OR) ¼ 0.54 (0.35, 0.84); 0.0024 with OR ¼ 0.77 (0.66, 0.91); 0.018 with OR ¼ 1.38 (1.06, 1.81); and 0.028 with OR ¼ 0.46 (0.23, 0.92) for alcohol, heroin, cocaine, and methamphetamine dependence/abuse, respectively). When all the phenotypes are combined, the P-value was 0.0006 with OR ¼ 0.86 (0.78, 0.94) in the combined European, Asian, and Mexican populations and P-value was 0.0028 with OR ¼ 1.41 (1.13, 1.78) in the African populations. Evidence of significant associations was also identified in other subgroup analyses regarding differently combined substance and populations. The effect sizes of 5-HTTLPR were comparable among the European, Asian, and Mexican populations, however, the risk allele was more frequent in Asians than in Europeans and Mexicans. The opposite directions of risk allele in African population might be driven by the opposite directions of risk allele in cocaine dependence. This meta-analysis supports that the association of the SLC6A4 gene with substance use disorder varies depending on substances with different risk allele frequencies in the multi-cultural populations. Further studies using larger sample size are warranted.

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Section: Introductionmentioning

confidence: 99%

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Cao

Hudziak

2013

Neuropsychopharmacol

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“…Only males showed an association to hypocortisolism when categorizing in a gender within SNP manner for both rs2185706 Zlojutro et al, 2011). As such, it should follow that SNP genotypes and haplotypes in the HTR7 gene should also be associated with changes in the stress response, resulting in an effect on immune function.…”

Section: Resultsmentioning

confidence: 99%

Genetic polymorphisms in the serotonin receptor 7 (HTR7) gene are associated with cortisol levels in African American young adults

et al. 2017

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Serotonin is a neurohormone involved in biological processes, Introduction: such as behavior and immune function. Chronic psychosocial stressors may cause serotonin release resulting in immune system dysregulation, as evidenced by increased or far decreased levels of cortisol, a blood biomarker of stress and immune function. We hypothesize that genetic polymorphisms in the gene are associated with both hypo-and hyper-cortisolism. HTR7Methods: The study population included 602 African American subjects between 18-34 years of age, living in Washington, D.C. Five single nucleotide polymorphisms (SNPs) in , rs2420367, rs12412496, rs2185706, rs7089533, and HTR7 rs7093602 were genotyped by restriction fragment length polymorphism or the TaqMan assay. Statistical analysis, using the program SNPstat, was performed to determine their associations with cortisol measured in the study population.While an increased risk of hypocortisolism was found to be associated Results: with rs2420367, rs2185706, and rs7093602 in a gender specific manner, no genotypes could be associated with hypercortisolism. Inversely, a decreased risk of hypocortisolism was found with the haplotype CGGCC (p=0.033), which remained significant in males. When adjusting for gender, females associated with the haplotype AGACC. Hypercortisolism was also associated with a decreased risk for the haplotypes AAACC (p=0.042) and AAGTT (p=0.001).Based on these results, genetic variation in the gene may Discussion: HTR7 contribute to both stress and inflammation, and will provide a new glimpse into stress-related inflammation psychophysiology.

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“…27; February 2009) and ‘tag SNP Picker' [the settings were the following: (1) population: Japanese in Tokyo; (2) pairwise methods: tagger pairwise; (3) R 2 cutoff: 0.8, and (4) MAF cutoff: 0.2] [46]. As a result, seven SNPs were extracted, and among them we selected rs791640, which has already been studied in several previous studies [47,48]. Rs1935349 was selected since it had a validated assay in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Takekita

Fabbri²,

Kato³

et al. 2015

Neuropsychobiology

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Background: Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japanese schizophrenia. Methods: Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. Results: Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). Conclusion: Our results show that HTR7 variants are not related to the overall improvement in schizophrenia symptoms.

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Genome‐wide association study of theta band event‐related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence

Cited by 71 publications

References 110 publications

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Genetic polymorphisms in the serotonin receptor 7 (HTR7) gene are associated with cortisol levels in African American young adults

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

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