Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD (original) (raw)

2012, American Journal of Psychiatry

1 8 6 a jp.p sych ia tryo n lin e.o rg A m J Psych ia try 1 6 9 :2 , Feb ru a ry 2 0 1 2 significance , although, as has repeatedly been demonstrated for other phenotypes, this can in part be overcome for at least a proportion of risk variants as larger samples become available for performing meta-analyses. For GWAS of childhood-onset psychiatric disorders, such as ADHD and autism, the types of sample sizes required, even with international collaboration, have yet to be achieved . Another possibility is that if ADHD is genetically heterogeneous (in the sense that there are multiple phenotypes with limited or no overlap at the level of common risk alleles), the effects of each allele might be diluted, resulting in lower apparent effect sizes. However, it is currently unclear how best to subdivide ADHD in a way that might overcome this problem or whether such subdivisions are possible. An alternative explanation for the negative GWAS findings might be that ADHD risk is entirely explained by multiple low-frequency variants that are not well captured by (A m J P sy c h ia try 2 0 1 2 ; 1 6 9 : in v e stig a tin g th e C o n trib u tio n o f C o m m o n G e n e tic V a ria n ts to th e r isk a n d P a th o g e n e sis o f A D H D