A linkage study of depression spectrum disease: the use of the sib-pair method.

Genetic linkage was studied in depression spectrum disease, a subgroup of unipolar depressive illness defined by presence of familial alcoholism and/or antisocial personality, using a version of the sib pair method of Penrose. Rigorous research diagnostic criteria were used and the diagnoses were made blind, i.e., without knowledge of the genetic marker results. Possibility of linkage was suggested (p less than 0.005) with the alpha-haptoglobin (alpha-Hp) and third complement component (C3) loci. However, the likelihood that these two markers are not on the same chromosome, and the limitations of the sib pair method, permit these findings to be treated as suggestive only and indicate that these two promising markers should be investigated further, using a more definitive method of linkage detection such as the lod score method.