Schizophrenia (SZ) is a common, devastating, incurable illness. By identifying its causes, we may understand its biological underpinnings better. SZ is highly heritable, but the precise genetic factors are obscure. Prior gene mapping studies have focused on the diagnosis alone, and cannot be expected to identify all the major susceptibility genes. To complement this work, we propose to investigate quantitative traits associated with the risk for SZ. Neurological examination abnormalities (NEAS) are more prevalent among persons with SZ in comparison with appropriate controls. Some studies have also reported that NEAs are more frequent among unaffected relatives of patients, suggesting that NEAs may be related to SZ risk. We have found that some NEAs are highly heritable among families of patients with SZ. However, it is uncertain whether our participants differ from controls, as NEA data are unavailable from suitable comparison individuals. We request support to ascertain and comprehensively evaluate 110 control individuals. Recruitment has commenced (n = 26 participants). Funds are required to complete the recruitment. Simultaneously, and at no additional cost, we will enlarge our sample of patients and their relatives (total of 330 participants from 55 families, average of five relatives/family). We will contrast these individuals with the controls. We will thus identify NEAs that distinguish the relatives of the patients from the control individuals, identify case-control differences and estimate heritability. Such traits may be considered 'endophenotypes' and could serve as covariates in our ongoing linkage/association studies. Successful identification of quantitative NEAs associated with SZ risk will also enable future genome-wide linkage analyses of these traits. Public health relevance: Our study will enable a better understanding of the relationship between neurological abnormalities and SZ. It may also enable us to identify precise genetic causes of schizophrenia, paving the way for better treatment. This is a competing supplement for MH 56242, 'Genetic Susceptibility in Schizophrenia'. ? ? ?
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