This study investigates the effects of XKR4, a recently identified candidate 
gene for Attention-Deficit/Hyperactivity Disorder (ADHD), birth weight, and 
their interaction on brain volume in ADHD. XKR4 is expressed in cerebellum and 
low birth weight has been associated both with changes in cerebellum and with 
ADHD, probably due to its relation with prenatal adversity. Anatomical MRI scans 
were acquired in 58 children with ADHD and 64 typically developing controls and 
processed to obtain volumes of cerebrum, cerebellum and gray and white matter in 
each structure. DNA was collected from saliva. Analyses including data on birth 
weight were conducted in a subset of 37 children with ADHD and 51 controls where 
these data were retrospectively collected using questionnaires. There was an 
interaction between genotype and birth weight for cerebellum gray matter volume 
(p = .020). The combination of homozygosity for the G-allele (the allele 
previously found to be overtransmitted in ADHD) and higher birth weight was 
associated with smaller volume. Furthermore, birth weight was positively 
associated with cerebellar white matter volume in controls, but not ADHD 
(interaction: p = .021). The interaction of genotype with birth weight affecting 
cerebellum gray matter is consistent with models that emphasize increased 
influence of genetic risk-factors in an otherwise favorable prenatal 
environment. The absence of an association between birth weight and cerebellum 
white matter volume in ADHD suggests that other genetic or environmental effects 
may be at play, unrelated to XKR4. These results underscore the importance of 
considering environmental effects in imaging genetics studies.