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

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          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.

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          Author and article information

          Journal
          Am. J. Med. Genet. B Neuropsychiatr. Genet.
          American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
          1552-485X
          1552-4841
          Mar 2014
          : 165B
          : 2
          Affiliations
          [1 ] MRC Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
          Article
          NIHMS634828
          10.1002/ajmg.b.32217
          4234115
          24482242
          73951aec-db4a-4f2a-a0a8-5d726da340be
          © 2014 Wiley Periodicals, Inc.
          History

          inbreeding,major depression,recessive risk model,runs of homozygosity

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