LINKAGE STUDIES SUGGEST A POSSIBLE LOCUS FOR BIPOLAR DISORDER NEAR THE VELO-CARDIO-FACIAL SYNDROME REGION ON CHROMOSOME-22

Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characteriz ed by multiple dysmorphisms, cleft palate, cardiac anomalies, and lear ning disabilities, that results from a microdeletion of chromosome 22q 11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American po pulation (University of California, San Diego/University of British Co lumbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A ma ximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod sco res of 1.68 and 1.28 were obtained at this marker under dominant and r ecessive models, respectively. Four additional markers were subsequent ly typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sib-pair an alyses were similarly positive in the UCSD/UBC families (P = 0.017), a nd in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chrom osome 22. (C) 1997 Wiley-Liss, Inc.