A recessive genetic model and runs of homozygosity in major depressive disorder

Power, Robert A., Keller, Matthew C., Ripke, Stephan, Abdellaoui, Abdel, Wray, Naomi R., Sullivan, Patrick F. and Breen, Gerome (2014) A recessive genetic model and runs of homozygosity in major depressive disorder. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 165 2: 157-166. doi:10.1002/ajmg.b.32217

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Author Power, Robert A.
Keller, Matthew C.
Ripke, Stephan
Abdellaoui, Abdel
Wray, Naomi R.
Sullivan, Patrick F.
Breen, Gerome
Title A recessive genetic model and runs of homozygosity in major depressive disorder
Journal name American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics   Check publisher's open access policy
ISSN 1552-4841
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/ajmg.b.32217
Open Access Status File (Author Post-print)
Volume 165
Issue 2
Start page 157
End page 166
Total pages 10
Place of publication Hoboken, NJ United States
Publisher John Wiley and Sons Inc.
Language eng
Subject 2716 Genetics (clinical)
2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
Abstract Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here, we explore the possibility of such a recessive model in MDD. In a sample of 9,238 cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS we perform an analysis of ROH and common variants under a recessive model. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (P=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD.
Keyword Inbreeding
Major depression
Recessive risk model
Runs of homozygosity
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID MH085520
01GS08144 01GS08147
U54 RR020278
FKZ 01GS0481
ERC 230374
QLG2-CT- 2002-01254
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
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