A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE)

Hiba Alblooshi, Habiba Al Safar, Holly F. Fisher, Heather J. Cordell, Ahmed El Kashef, Hamad Al Ghaferi, Mansour Shawky, Stuart Reece, Gary K. Hulse, Guan K. Tay

Research output: Contribution to journalArticle

Abstract

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10−8), rs74477937 (p-value = 8.56 × 10−8) and rs78707086 (p-value = 8.55 × 10−8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

Original languageEnglish
Pages (from-to)68-79
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume180
Issue number1
Early online date16 Dec 2018
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

United Arab Emirates
Genome-Wide Association Study
Substance-Related Disorders
Chromosomes
Single Nucleotide Polymorphism
Registries
Meta-Analysis
Population
Genes

Cite this

@article{36c48e1a18e2419abc0f981477d58a34,
title = "A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE)",
abstract = "Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10−8), rs74477937 (p-value = 8.56 × 10−8) and rs78707086 (p-value = 8.55 × 10−8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.",
keywords = "chromosome 7, genome wide association study (GWAS), substance use disorder (SUD), translation, UAE",
author = "Hiba Alblooshi and {Al Safar}, Habiba and Fisher, {Holly F.} and Cordell, {Heather J.} and {El Kashef}, Ahmed and {Al Ghaferi}, Hamad and Mansour Shawky and Stuart Reece and Hulse, {Gary K.} and Tay, {Guan K.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ajmg.b.32708",
language = "English",
volume = "180",
pages = "68--79",
journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss",
number = "1",

}

A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE). / Alblooshi, Hiba; Al Safar, Habiba; Fisher, Holly F.; Cordell, Heather J.; El Kashef, Ahmed; Al Ghaferi, Hamad; Shawky, Mansour; Reece, Stuart; Hulse, Gary K.; Tay, Guan K.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 180, No. 1, 01.01.2019, p. 68-79.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE)

AU - Alblooshi, Hiba

AU - Al Safar, Habiba

AU - Fisher, Holly F.

AU - Cordell, Heather J.

AU - El Kashef, Ahmed

AU - Al Ghaferi, Hamad

AU - Shawky, Mansour

AU - Reece, Stuart

AU - Hulse, Gary K.

AU - Tay, Guan K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10−8), rs74477937 (p-value = 8.56 × 10−8) and rs78707086 (p-value = 8.55 × 10−8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

AB - Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10−8), rs74477937 (p-value = 8.56 × 10−8) and rs78707086 (p-value = 8.55 × 10−8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

KW - chromosome 7

KW - genome wide association study (GWAS)

KW - substance use disorder (SUD)

KW - translation

KW - UAE

UR - http://www.scopus.com/inward/record.url?scp=85058567834&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32708

DO - 10.1002/ajmg.b.32708

M3 - Article

VL - 180

SP - 68

EP - 79

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 1

ER -