Supplementary Material for: A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation

<p>Mitochondrial DNA mutations have been reported to be associated with bipolar disorder (BD). In this study, we performed genome-wide analyses to assess mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early-onset BD (EOBD) among BD patients, focusing on interaction effects between nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European American BD cases (<i>n</i> = 1,001) and controls (<i>n</i> = 1,034) from the Genetic Association Information Network BD study were analyzed to assess the joint effect of nSNP and nSNP-mtSNP interaction on the risk of BD and EOBD. The effect of nSNP-mtSNP interactions was also assessed. For BD risk, the strongest evidence of an association was obtained for nSNP rs1880924 in <i>MGAM</i> and mtSNP rs3088309 in <i>CytB</i> (<i>p</i><sub>joint</sub> = 8.2 × 10<sup>-8</sup>, <i>p</i><sub>int</sub> = 1.4 × 10<sup>-4</sup>). Our results also suggest that the minor allele of the nSNP rs583990 in <i>CTNNA2</i> increases the risk of EOBD among carriers of the mtSNP rs3088309 minor allele, while the nSNP has no effect among those carrying the mtSNP major allele (OR = 4.53 vs. 1.05, <i>p</i><sub>joint</sub> = 2.1 × 10<sup>-7</sup>, <i>p</i><sub>int</sub> = 1.16 × 10<sup>-6</sup>). While our results are not statistically significant after multiple testing correction and a large-sample replication is required, our exploratory study demonstrates the potential importance of considering the mitochondrial genome for identifying genetic factors associated with BD.</p>