Stratified analyses of genome wide association study data reveal haplotypes for a candidate gene on chromosome 2 (KIAA1211L) is associated with opioid use in patients of Arabian descent

Abstract

Background: Genome Wide Association Studies (GWAS) have been conducted to identify genes and pathways involved in development of opioid use disorder. This study extends the first GWAS of substance use disorder (SUD) patients from the United Arab Emirates (UAE) by stratifying the study group based on opioid use, which is the most common substance of use in this cohort. Methods: The GWAS cohort consisted of 512 (262 case, 250 controls) male participants from the UAE. The samples were genotyped using the Illumina Omni5 Exome system. Data was stratified according to opioid use using PLINK. Haplotype analysis was conducted using Haploview 4.2. Results: Two main associations were identified in this study. Firstly, two SNPs on chromosome 7 were associated with opioid use disorder, rs118129027 (p-value = 1.23 × 10 − 8) and rs74477937 (p-value = 1.48 × 10 − 8). This has been reported in Alblooshi et al. (Am J Med Genet B Neuropsychiatr Genet 180(1):68-79, 2019). Secondly, haplotypes on chromosome 2 which mapped to the KIAA1211L locus were identified in association with opioid use. Five SNPs in high linkage disequilibrium (LD) (rs2280142, rs6542837, rs12712037, rs10175560, rs11900524) were arranged into haplotypes. Two haplotypes GAGCG and AGTTA were associated with opioid use disorders (p-value 3.26 × 10 − 8 and 7.16 × 10 − 7 , respectively). Conclusion: This is the first GWAS to identify candidate genes associated with opioid use disorder in participants from the UAE. The lack of other genetic data of Arabian descent opioid use patients has hindered replication of the findings. Nevertheless, the outcomes implicate new pathways in opioid use disorder that requires further research to assess the role of the identified genes in the development of opioid use disorder.

Meta-analyses of genome wide association studies in lines of laying hens divergently selected for feather pecking using imputed sequence level genotypes

“…Inspecting the genes in our meta-analysis, using VEP revealed that NIPA1, KIAA1211L, AFF3, and TSGA10 are genes affected by variants in this region. Copy number variations in NIPA1 were found in psychiatric disorders [39], KIAA1211L was identified in a schizophrenia twin-study [40] and is a candidate gene for opioid abuse [41], and AFF3 is involved in intellectual disability and cellular migration in the cerebral cortex of mice [42]. The studies mentioned make those genes likely candidates to influence the trait pEFP.…”

“…Concerning the trait pEFP we could confirm a QTL on GGA1 that was previously identified [6], which in our study contains variants affecting NIPA1, KIAA1211L, AFF3, and TSGA10. All of those genes, except TSGA10, have been implicated in neurological conditions [39][40][41][42] making them additional targets for genomic selection against FP.…”

lncRNA Sequencing Reveals Neurodegeneration-associated FUS Mutations Alter Transcriptional Landscape of iPS Cells That Persists In Motor Neurons

“…CRACD downregulation has been strongly associated with various types of cancer and metastasis, including small cell lung carcinoma 41 , and colorectal cancer stem cells 42 . Haplotypes of CRACD have been linked to opioid use in patients, as indicated by a recent genome-wide association study (GWAS) 43 . During development, CRACD is expressed during early timepoints and is thought to play a role in tissue differentiation, particularly in the heart and both peripheral and central nervous systems.…”

lncRNA Sequencing Reveals Neurodegeneration-Associated FUS Mutations Alter Transcriptional Landscape of iPS Cells That Persists in Motor Neurons

“…CRACD downregulation has been strongly associated with various types of cancer and metastasis, including small-cell lung carcinoma [60] and colorectal cancer stem cells [61]. Haplotypes of CRACD have been linked to opioid use in patients, as indicated by a recent genome-wide association study (GWAS) [62]. During development, CRACD is expressed during early timepoints and is thought to play a role in tissue differentiation, particularly in the heart and both the peripheral and central nervous systems.…”