Genome-wide scan of homogeneous subtypes of NIMH genetics initiative schizophrenia families

Abstract

In the light of the potential etiological heterogeneity of schizophrenia, we reanalyzed the NIMH genetics initiative data for schizophrenia. We performed linkage analyses on schizophrenia families divided into more homogeneous subgroups. The African-American and European-American families were divided into groups that were successively more homogeneous. The first group included schizophrenia families that were highly familial, meaning that they contained a minimum specified number of affected individuals. We also excluded patients with environmental influences that may affect disease status. These influences included obstetric complications (OC) and viral infections during the neurodevelopmental stage (VIN). In the African-American sample, a linkage analysis of highly familial schizophrenia families without any environmental influences resulted in a single-point LOD (SLOD) score of 2.90, a multipoint LOD (MLOD) of 2.11, a single-point heterogeneity LOD (SHLOD) score of 3.04, and a multipoint heterogeneity LOD (MHLOD) score of 2.11 at marker D8S1819 (8p23.1) under a dominant parametric model. The highly familial European-American schizophrenia families resulted in an SLOD of 0.91 and an MLOD of 1.85, an SHLOD of 1.64 and an MHLOD of 1.97 at marker D22S1169 (22q13.32) using a recessive parametric model. Although this work should be interpreted cautiously and requires replication, these results suggest that schizophrenia may be linked to chromosomal regions 8p23.1 and 22q12.3–q13.32.