Repeat expansions in neuropsychiatric disorders

We have analyzed a number of neuropsychiatric disorders that display anticipation for the presence of expanded DNA sequences. CAG/CTG trinucleotide repeat expansions (TRE) have previously been detected in bipolar disorder using the repeat expansion detection (RED) method. We found that 89% of RED products (CAG/CTG repeats) >120 nt (n = 202) detected in affective disorder patients as well as unaffected family members and controls from Northern Sweden correlate with expansions at two repeat loci, ERDA1 on chromosome 17q21.3 and CTG18.1 on 18q21.1. In a previously studied material, the frequency of expansions at the CTG18.1 locus was 13% in bipolar patients (n = 60) and 5% in controls (n = 114) (P < 0.07) with a significantly different size distribution (P < 0.03). A second set of patients were ascertained from 14 affective disorder families showing anticipation. In these families, the RED product distribution was significantly different (P < 0.0007) between affected (n = 53) and unaffected (n = 123) offspring. A higher frequency (P < 0.04) of CTG18.1 expansions as well as a different (P < 0.02) repeat size distribution was seen between affected and unaffected offspring. In addition, a negative correlation between RED product size and the age of onset could be seen in affected offspring (rs = -0.3, P = 0.05, n = 43). No difference in ERDA1 expansion frequency was seen either between bipolar patients (35%, n = 60) and matched controls (29%, n = 114), or between affected and unaffected offspring in the families. We conclude that expanded alleles at the CTG18.1 locus give an odds ratio slightly below 3 and may thus act as a vulnerability factor for affective disorder.