Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
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Author
Zlojutro, MarkManz, Niklas
Rangaswamy, Madhavi
Xuei, Xiaoling
Flury-Wetherill, Leah
Koller, Daniel
Bierut, Laura J
Goate, Alison
Hesselbrock, Victor
Kuperman, Samuel
Nurnberger, John
Rice, John P
Schuckit, Marc A
Foroud, Tatiana
Edenberg, Howard J
Porjesz, Bernice
Almasy, Laura
Journal title
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric GeneticsDate Published
2010-11-02Publication Volume
156BPublication Issue
1Publication Begin page
44Publication End page
58
Metadata
Show full item recordAbstract
Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10⁻⁶). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10⁻⁴), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.Citation
Zlojutro M, Manz N, Rangaswamy M, Xuei X, Flury-Wetherill L, Koller D, Bierut LJ, Goate A, Hesselbrock V, Kuperman S, Nurnberger J Jr, Rice JP, Schuckit MA, Foroud T, Edenberg HJ, Porjesz B, Almasy L. Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):44-58. doi: 10.1002/ajmg.b.31136. Epub 2010 Nov 2. PMID: 21184583; PMCID: PMC3139811.DOI
10.1002/ajmg.b.31136ae974a485f413a2113503eed53cd6c53
10.1002/ajmg.b.31136
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- Creative Commons
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