title: Possible involvement of the circadian pathway in alcohol use disorder in a South African adolescent cohort.
abstract: Alcoholism has an estimated heritability of between 40 and 60% and it is thought that several genes of small effect may contribute to the risk of developing this disorder. Studies of the genetics of alcohol use disorder (AUD) may, however, be confounded by issues of comorbidity. The aim of this investigation was to assess associations between variants in a range of candidate genes and AUD in a unique sample of adolescents without comorbidity. Our cohort consisted of 80 adolescents with an AUD diagnosis and 80 matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 SNPs in 378 candidate genes. Association analysis, gene-based analysis and polygenic scoring were performed. There was no statistical association between any of the investigated SNPs and AUD after correction for multiple testing. However, from the gene-based analysis it was found that the circadian rhythm genes NR1D1 and BHLHE41 are associated with AUD. While preliminary, these data provide some evidence that the circadian pathway may be relevant to the pathophysiology of AUD. Study of early onset non-comorbid populations with AUD may be useful in identifying target genes for study in larger more representative samples.
authors.affiliation: MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. dlvsha006@myuct.ac.za.
authors.forename: Shareefa
authors.initials: S
authors.lastname: Dalvie
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: King
authors.affiliation: Neurobehavioral Research Inc., Honolulu, HI, USA.
authors.forename: George
authors.initials: G
authors.lastname: Fein
authors.affiliation: MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Raj
authors.initials: R
authors.lastname: Ramesar
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D044383:Black People; D002940:Circadian Rhythm / Q000235:genetics*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000523:psychology; D020641:Polymorphism, Single Nucleotide; D013019:South Africa
keywords: Alcoholism; Circadian; Single nucleotide polymorphism