For the Narrow (recurrent early-onset) phenotype, the strongest signal was in chromosome 18q22.1. The SNP with the lowest P-value had low imputation r2 values, but two other nearby SNPs had P-values less than 10−5. This region has previously been of interest in linkage studies of both bipolar disorder and MDD (see discussion in the companion paper4), and given that support for this region varied widely across our three samples, one might wonder whether they differed with respect to bipolar features, but we lacked the relevant data to compare the datasets. GenRED provided the strongest support and also had the most specific procedures to exclude bipolar disorder in probands and relatives, although the severe, recurrent, early-onset phenotype more closely resembles bipolar disorder. The next strongest signals were in a non-genic region of 5p13.2, 220kb upstream of GDNF; and in a cluster of histone genes on 6p22.1, in the same region where significant association to schizophrenia was recently observed.12–14 The latter finding was detected in a meta-analysis that included MGS, using a superset of the GenRED/STAR*D controls. However, MGS contributed very little of the statistical support for 6p22.1 association to schizophrenia.
