KAT2B Polymorphism Identified for Drug Abuse in African Americans with Regulatory Links to Drug Abuse Pathways in Human Prefrontal Cortex
Abstract
Drug abuse is a common and heritable set of disorders, but the underlying genetic factors are largely unknown. We conducted genome‐wide association studies of drug abuse using 7 million imputed single nucleotide polymorphisms (SNPs) and insertions/deletions in African Americans (AAs; n = 3742) and European Americans (EAs; n = 6845). Cases were drawn from the Urban Health Study of street‐recruited people, who injected drugs and reported abusing opioids, cocaine, marijuana, stimulants and/or other drugs 10 or more times in the past 30 days, and were compared with population controls. Independent replication testing was conducted in 755 AAs and 1131 EAs from the Genetic Association Information Network. An intronic SNP (rs9829896) in the K(lysine) acetyltransferase 2B (KAT2B) gene was significantly associated with drug abuse in AAs (P = 4.63 × 10−8) and independently replicated in AAs (P = 0.0019). The rs9829896‐C allele (frequency = 12%) had odds ratios of 0.68 and 0.53 across the AA cohorts: meta‐analysis P = 3.93 × 10−10. Rs9829896‐C was not associated with drug abuse across the EA cohorts: frequency = 36% and meta‐analysis P = 0.12. Using dorsolateral prefrontal cortex data from the BrainCloud cohort, we found that rs9829896‐C was associated with reduced KAT2B expression in AAs (n = 113, P = 0.050) but not EAs (n = 110, P = 0.39). KAT2B encodes a transcriptional regulator in the cyclic adenosine monophosphate and dopamine signaling pathways, and rs9829896‐C was associated…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 6,845 participants or records.
Read the paper
Related studies
- Diagnosis and management of glutaric aciduria type I – revised recommendations
- EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
- Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
- Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.