Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans

Biological Psychiatry
Zhongshan ChengJoel Gelernter

Abstract

Opioid dependence (OD) is at epidemic levels in the United States. Genetic studies can provide insight into its biology. We completed an OD genome-wide association study in 3058 opioid-exposed European Americans, 1290 of whom met criteria for a DSM-IV diagnosis of OD. Analysis used DSM-IV criterion count. By meta-analysis of four cohorts, Yale-Penn 1 (n = 1388), Yale-Penn 2 (n = 996), Yale-Penn 3 (n = 98), and SAGE (Study of Addiction: Genetics and Environment) (n = 576), we identified a variant on chromosome 15, rs12442183, near RGMA, associated with OD (p = 1.3 × 10-8). The association was also genome-wide significant in Yale-Penn 1 taken individually and nominally significant in two of the other three samples. The finding was further supported in a meta-analysis of all available opioid-exposed African Americans (n = 2014 [1106 meeting DSM-IV OD criteria]; p = 3.0 × 10-3) from three cohorts; there was nominal significance in two of these samples. Thus, of seven subsamples examined in two populations, one was genome-wide significant, and four of six were nominally (or nearly) significant. RGMA encodes repulsive guidance molecule A, which is a central nervous system axon guidance protein. Risk allele rs12442183*T was correlated...Continue Reading

Citations

Mar 16, 2019·Scientific Reports·Janitza L Montalvo-OrtizJoel Gelernter
Jul 31, 2019·Addiction Biology·Zhongshan ChengJoel Gelernter
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