Journal article
Genome-Wide Association Study of Theta Band Event-Related Oscillations Identifies Serotonin Receptor Gene HTR7 Influencing Risk of Alcohol Dependence
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.156(1), pp.44-58
01/2011
DOI: 10.1002/ajmg.b.31136
PMCID: PMC3139811
PMID: 21184583
Abstract
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 1M 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.
Details
- Title: Subtitle
- Genome-Wide Association Study of Theta Band Event-Related Oscillations Identifies Serotonin Receptor Gene HTR7 Influencing Risk of Alcohol Dependence
- Creators
- Mark Zlojutro - Department of Psychiatry, University of California, San Diego, CaliforniaNiklas Manz - Department of Psychiatry, University of California, San Diego, CaliforniaMadhavi Rangaswamy - Department of Psychiatry, University of California, San Diego, CaliforniaXiaoling Xuei - Department of Psychiatry, University of California, San Diego, CaliforniaLeah Flury-Wetherill - Department of Psychiatry, University of California, San Diego, CaliforniaDaniel Koller - Department of Psychiatry, University of California, San Diego, CaliforniaLaura J Bierut - Department of Psychiatry, University of California, San Diego, CaliforniaAlison Goate - Department of Psychiatry, University of California, San Diego, CaliforniaVictor Hesselbrock - Department of Psychiatry, University of California, San Diego, CaliforniaSamuel Kuperman - Department of Psychiatry, University of California, San Diego, CaliforniaJohn Nurnberger - Department of Psychiatry, University of California, San Diego, CaliforniaJohn P Rice - Department of Psychiatry, University of California, San Diego, CaliforniaMarc A Schuckit - Department of Psychiatry, University of California, San Diego, CaliforniaTatiana Foroud - Department of Psychiatry, University of California, San Diego, CaliforniaHoward J Edenberg - Department of Psychiatry, University of California, San Diego, CaliforniaBernice Porjesz - Department of Psychiatry, University of California, San Diego, CaliforniaLaura Almasy - Department of Psychiatry, University of California, San Diego, California
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.156(1), pp.44-58
- DOI
- 10.1002/ajmg.b.31136
- PMID
- 21184583
- PMCID
- PMC3139811
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- U10 AA008401-23 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 01/2011
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003452202771
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