In 1999, Detera-Wadleigh et al. reported suggestive linkage to 1q31-32 in a genome-wide scan of 22 pedigrees. However, few recent studies have found linkage signals to chromosome 1 that meet standard criteria for significance (Lander and Kruglyak 1995). Ewald et al. (2002b) examined two families of bipolar probands of Danish Caucasian origin for genome-wide linkage using narrow and broad phenotypic models.
Two-point parametric analyses were conducted by using LINKAGE (Lathrop et al. 1984). Under a broad model, parametric analyses yielded a suggestive two-point LOD score of 2.75 for affected members only in both families at D1S216, and a follow-up three-point analysis detected an increased LOD score of 2.98. However, given that this sample consisted of only two families, these findings should be taken with caution.
In a genome-wide survey, Curtis et al. (2003) examined seven British and Icelandic pedigrees affected with multiple cases of bipolar disorder and unipolar depression, diagnosed by using the RDC (Spitzer et al. 1978). A total of 365 microsatellite markers were used, and VITESSE (O'Connell and Weeks 1995) was used for LOD score analyses. Bipolar depression, unipolar depression, and combined models were run assuming dominant or recessive transmission, for a total of 6 LOD score analyses. Results suggest a potential vulnerability locus in the region of marker D1S251; a four-point LOD score analysis revealed a suggestive peak heterogeneity LOD score of 2.0 under a combined, dominant model. The findings from both Ewald et al. (2002b) and Curtis et al. (2003) are consistent with earlier reports from the NIMH Genetics Initiative bipolar survey (Rice et al. 1997; Detera-Wadleigh et al. 1999).
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