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- Balachander, S, et al.
(author)
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Are There Familial Patterns of Symptom Dimensions in Obsessive-Compulsive Disorder?
- 2021
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In: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 651196-
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Journal article (peer-reviewed)abstract
- Background:Obsessive-compulsive disorder (OCD) is a heterogeneous illness, and emerging evidence suggests that different symptom dimensions may have distinct underlying neurobiological mechanisms. We aimed to look for familial patterns in the occurrence of these symptom dimensions in a sample of families with at least two individuals affected with OCD.Methods:Data from 153 families (total number of individuals diagnosed with DSM-5 OCD = 330) recruited as part of the Accelerator Program for Discovery in Brain Disorders using Stem Cells (ADBS) was used for the current analysis. Multidimensional Item Response Theory (IRT) was used to extract dimensional scores from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) checklist data. Using linear mixed-effects regression models, intra-class correlation coefficients (ICC), for each symptom dimension, and within each relationship type were estimated.Results:IRT yielded a four-factor solution with Factor 1 (Sexual/Religious/Aggressive), Factor 2 (Doubts/Checking), Factor 3 (Symmetry/Arranging), and Factor 4 (Contamination/Washing). All except for Factor 1 were found to have significant ICCs, highest for Factor 3 (0.41) followed by Factor 4 (0.29) and then Factor 2 (0.27). Sex-concordant dyads were found to have higher ICC values than discordant ones, for all the symptom dimensions. No major differences in the ICC values between parent-offspring and sib-pairs were seen.Conclusions:Our findings indicate that there is a high concordance of OCD symptom dimensions within multiplex families. Symptom dimensions of OCD might thus have significant heritability. In view of this, future genetic and neurobiological studies in OCD should include symptom dimensions as a key parameter in their analyses.
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| 2. |
- Ganesh, S, et al.
(author)
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Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
- 2022
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 21128-
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Journal article (peer-reviewed)abstract
- Whole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrelated controls. Within pedigree prioritization employed criteria of rarity, functional consequence, and sharing by ≥ 3 affected members. Across the sample, gene and gene-set-wide case–control association analysis was performed with Sequence Kernel Association Test (SKAT). In 14/16 families with ≥ 3 sequenced affected individuals, we identified a total of 78 rare predicted deleterious variants in 78 unique genes shared by ≥ 3 members with SMI. Twenty (25%) genes were implicated in monogenic CNS syndromes in OMIM (OMIM-CNS), a fraction that is a significant overrepresentation (Fisher’s Exact test OR = 2.47, p = 0.001). In gene-set SKAT, statistically significant association was noted for OMIM-CNS gene-set (SKAT-p = 0.005) but not the synaptic gene-set (SKAT-p = 0.17). In this WES study in F-SMI, we identify private, rare, protein altering variants in genes previously implicated in Mendelian neuropsychiatric syndromes; suggesting pleiotropic influences in neurodevelopment between complex and Mendelian syndromes.
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