DRD5 – Attention Deficit Hyperactivity Disorder

Family‐based transmission disequilibrium testing (TDT) has revealed modest biased transmission of DRD5 microsatellite alleles in ADHD. In a Turkish trio cohort (n=104), a trend for linkage and association was reported (TDT χ2=2.38, one‐tailed P=0.06) with more significant association among methylphenidate responders (PMID:10889550). A larger multiplex family study confirmed biased nontransmission of the DRD5 146-bp allele (P=0.02) (PMID:14699430). However, adult ADHD severity analyses (n=110) and a Colombian trio/case–control study (n=152) found no significant DRD5 associations (PMID:20006992; PMID:26526368). Rare copy number variants overlapping the DRD5 locus were observed in 7.7% of ADHD probands (19/248) but absent in 2,357 controls (PMID:21832240). Age at onset analyses in 229 families identified SNP haplotypes flanking DRD5 associated with earlier ADHD onset (FDR‐adjusted q<0.023) (PMID:17501935).

Overall, DRD5 associations rely on small family cohorts, common regulatory and structural variants, and lack pathogenic coding changes or segregation data. Replication is inconsistent across populations. Key Take-home: Current evidence is limited for DRD5 variants as diagnostic or predictive markers in ADHD.

References

• Molecular psychiatry | 2000 | Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. PMID:10889550
• Molecular psychiatry | 2004 | Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. PMID:14699430
• Journal of psychiatric research | 2010 | Correlation of a set of gene variants, life events and personality features on adult ADHD severity. PMID:20006992
• Annals of neurosciences | 2015 | Lack of association of polymorphisms in six candidate genes in Colombian ADHD patients. PMID:26526368
• Science translational medicine | 2011 | Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. PMID:21832240
• Annals of human genetics | 2007 | Evidence for an association of the dopamine D5 receptor gene on age at onset of attention deficit hyperactivity disorder. PMID:17501935

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