Biochemical and Biophysical Research Communications
Identification of high risk DISC1 structural variants with a 2% attributable risk for schizophrenia
Section snippets
Materials and methods
Patient and control samples. All 288 schizophrenics (274 Caucasian,14 African-American; 201 males, 87 females) met criteria for the disease as defined by the Diagnostic and Statistical Manual, Fourth Edition, Revised (DSM-IV-R), as described previously [30]. The majority of patients were ascertained through state mental institutions in Minnesota. Two hundred and eighty-eight controls for all Midwest Caucasian patients seen at the Mayo Clinic had no known history of psychiatric illness within
Cohort-specific structural variants dramatically increase schizophrenia risk
The regions of likely functional significance for the DISC1 gene were analyzed in 288 schizophrenia patients and 288 controls (“discovery scan”) (Fig. 1). Five megabases were analyzed in total. Fourteen unique structural variants were identified. Eight patients had seven unique variants found only in schizophrenia patients (cohort-specific) and one control had a variant found only in the normal controls (p < 0.02) (Table 1). Six structural variants occurred in both patients and controls (Table 2
Discussion
Five novel ultra-rare cohort-specific variants (R37W, S90L, T603I, G14A, and R418H) were found in six of 288 schizophrenia patients by sequencing the coding exons and splice junctions of the DISC1 gene (Fig. 2). None of these novel cohort-specific variants were found in 288 Caucasian controls in the discovery scan or in 10,000 unrelated control alleles in the gene pool screen (10,576 control alleles total).
Acknowledgments
We thank Jiesheng Chen for DNA sequencing, Shuya Hu and Cecile Katz for technical assistance, Dr. Carolyn Buzin for critical comments.
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