Chromosome 18q22.1 (Figure 2) has produced suggestive evidence for linkage to bipolar disorder in several studies41–47 (although not in the largest combined analysis48) and particularly in families with multiple bipolar-II (BP-II) cases43, 44 (characterized by recurrent depression plus hypomania). Several studies have also reported suggestive linkage to MDD or related personality traits in the same region.49 Study of a family with diverse mood disorders46 identified DSEL (dermatan sulfate epimerase-like), a brain-expressed gene in which two non-synonymous mutations were observed in cases but not in controls.50 Dermatan sulfate epimerase is involved in D-glucuronic acid metabolism and tumor rejection. The most strongly associated SNPs in the present study are upstream of DSEL, in regions with possible regulatory functions, and within an mRNA (BC053410), identified in pooled human brain tissue, that encodes a hypothetical protein (LOC643542) of unknown function. Familial co-aggregation of MDD and BP-II disorder has been inadequately studied. BP-II was an exclusion criterion for GenRED probands, although in GenRED I, BP-II was diagnosed in 4.2% of the siblings selected for interview because of a history of depression, so the prevalence among all siblings was lower.
