Higher polygenic risk for cardiovascular disease is associated with lower cerebral blood flow in youth with bipolar disorder

Bipolar disorder (BD) is associated with excess cardiovascular burden and anomalous cerebral blood flow (CBF). We examined coronary artery disease (CAD) and myocardial infarction (MI) polygenic risk scores (PRS) in relation to CBF among youth with BD. Participants (mean age 17.2 years; n = 63 BD, n = 41 healthy controls [HC]) underwent magnetic resonance imaging to quantify CBF using arterial spin labelling. CAD-PRS and MI-PRS were calculated using adult genome-wide association summary statistics. Covariate-adjusted voxel-wise analyses examined associations of CAD-PRS and MI-PRS with CBF in the combined sample, and within subgroups. Sex-stratified analyses and PRS-by-diagnosis interaction effects were also examined. Sensitivity analyses controlled for psychotropic medications, cardiovascular risk factors, and mood. Higher MI-PRS was associated with lower CBF in one occipital cluster (β = −0.44, p = 0.003) in the combined sample, and two frontal and one occipital cluster within BD (β range = −0.47 to −0.51, p range = 0.03 to