Objectives Inbreeding increases the probability of homozygosity of deleterious alleles. Inbreeding and runs of homozygosity (ROH) are associated with an increased risk for disease phenotypes, including schizophrenia and other psychiatric disorders. The effects of inbreeding, ROH, homozygous deletions, and other copy number variations (CNVs) on risk for depression and suicide attempt (SA) were quantified in an Arab Bedouin Kindred. Methods We carried out genetic analyses of 439 individuals from an Arab kindred with high rates of depression and suicidal behavior. We obtained complete ascertainment of SAs and first-degree relatives of individuals who have attempted or died by suicide. Results We found extensive regions of ROH. On average, 5% of the genome is covered by ROH for these individuals, two-fold higher than ROH rates for individuals from populations of European ancestry. Inbreeding and total length of ROH were not associated with risk for depression or attempt. For CNVs, an increased number of duplications more than 500 kb was associated with an increased risk for attempt (odds ratio: 2.9; P=0.01; 95% confidence interval: 1.3-6.6). Although not significant after correction for multiple testing, the risk for SA appears to increase with copy number for a CNV on chromosome 9p24.1. This possibility is intriguing because the CNV covers GLDC, which encodes glycine dehydrogenase that binds to glycine, a co-agonist at N-methyl-D-aspartate glutamate receptors, and is involved in glutamatergic neurotransmission. Conclusion Our findings add to the growing evidence of genetic risk factors that act pleiotropically to increase the risk for several neuropsychiatric disorders, including depression and SA, irrespective of ancestry.
|Number of pages||9|
|State||Published - 31 May 2017|
Bibliographical noteFunding Information:
This study work was supported by a K01 grant (MH077930, Melhem N.M.) from the National Institute of Mental Health, NARSAD Young Investigator Award (Melhem N.M.), Klingenstein Third Generation Foundation Postdoctoral Fellowship (Melhem N.M.), and grants from the Pittsburgh Foundation (Melhem N.M.), United States-Israel Binational Science Foundation (Apter A, Brent D), American Foundation for Suicide Prevention (Apter A), and Knut and Alice Wallenberg Foundation, Sweden (Wasserman D.).
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- Arab population
- Copy number variation
- Runs of homozygosity
- Suicidal behavior