Psychiatry Research 220 (2014) 722
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Letter to the Editor
Analysis of quantitative genetic characteristics of schizophrenia using combined allele frequency as a genetic marker To the Editors: In spite of the rapid pace of development of molecular technology and expansion of genome sequence information, schizophrenia (SCH) related genes have remained elusive, partly because of the use of inefficacious markers of qualitative genetic characteristics in previous studies. Another cause may be that although genetic liability results from the combined effects of multiple genes rather than the effect of a single gene, genetic screening tests for SCH have rarely targeted multiple SCH-related genes. To overcome these shortcomings, we considered multiple SCH-related genes as an integer for the screening of new, highly efficacious markers of quantitative genetic characteristics. DNA samples were collected from 150 SCH patients (78 men and 72 women; mean age, 28.978.9 years) and 200 healthy subjects (100 men and 100 women; mean age, 3876.2 years) in Dalian, China. The alleles at nine randomly selected Combined DNA Index System (CODIS) short tandem repeat (STR) loci, CODIS STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820), were determined using the AmpFLSTR Profiler plus PCR Amplification Kit and detailed information was recorded in literature for these loci (Deng et al., 2007; Hui et al., 2014). They were chosen in this study because of reliable assay and rich data source. The combined allele frequency (CAF) was defined as the probability of two alleles being located together at a single locus in an individual. Frequently combined alleles are considered conservative alleles, whereas infrequently combined alleles are considered mutable alleles. Thus, CAF can be considered as a continuous variable from conservation to mutation, and a quantitative genetic marker. CAF was calculated as follows: For heterozygotes,
the CAF for each locus as the independent variable. The results revealed that the CAFs of FGA, D21S11, D5S818 and D7S820 produced statistically significant regression equation (po0.05); D3S1358, D8S1179, vWA, D13S317 and D18S51 were removed from regression equation. The logistic regression equation was as follows: Y ¼ 0:327 0:086CAF FGA þ 0:115CAF D21S11 0:057CAF D5S818 0:044CAF D7S820 Probability value ¼ expðyÞ=½1 þ expðyÞ The probability value from the logistic regression could be considered a genetic marker and the quantitative genetic characteristic was observed in the SCH group and the normal population using ROC analysis. The area under the curve (AUC) was 0.663 (po0.0001). All analyses were performed using the SPSS 13.0 statistical software package. By using CAF as a quantitative genetic marker instead of a count marker (allele frequency), the efficacy of genetic analysis can be improved. This study demonstrates that at least four of the nine randomly selected CODIS STR loci were related to SCH, indicating that many SCH-associated genes may exist in the genome, and it may be difficult or impossible to identify all SCH-associated genes. The analysis of CAFs via our method may exemplify a different approach to estimate the quantitative genetic characteristics of SCH and provide a more efficient and reliable model to determine the genetic predispositions of an individual to these disorders with using studies of the Psychiatric Genomics Consortium. References Deng, YJ., Yan, JW., Yu, XG., Li, YZ., Mu, HF., Huang, YQ., Shi, XT., Sun, WM., 2007. Genetic analysis of 15 STR loci in Chinese Han population from West China. Genomics Proteomics Bioinformatics 5 (1), 66–69. Hui, L., Liping, G., Jian, Y., Laisui, Y., 2014. A new design without control population for identification of gastric cancer-related allele combinations based on interaction of genes. Gene 540, 32–36.
CAF ¼ 2 ðfrequency of allele 1 frequency of allele 2Þ 100 Yang Guang, Zhang Lei, Xiao Nan, Liu Hui n College of Medical Laboratory, Dalian Medical University, Dalian 116044, China E-mail addresses: [email protected], [email protected] (L. Hui)
For homozygotes, CAF ¼ ðfrequency of alleleÞ2 100 The above allele frequencies are expected to be present in a normal population. The allele frequencies for the nine loci in our study were previously determined in a population (n¼ 7636) from the same geographic region from which our study subjects were recruited (Deng et al., 2007). A more important aspect of CAF is the reduction of allele dimension; with CAF, only one variable can be used to describe the characteristic of a locus; thus, CAFs from many loci can be considered as an integer to directly use in multivariate analysis tools. In this study, the binary logistic regression analysis (backward method) was performed, with SCH (1) and control (0) as the dependent variables and http://dx.doi.org/10.1016/j.psychres.2014.08.038 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Xie Soufu, Xv Junting Dalian Seventh Hospital, Dalian 116000, China Received 11 May 2014 18 August 2014 20 August 2014
n
Corresponding author.
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Letter to the Editor
Analysis of quantitative genetic characteristics of schizophrenia using combined allele frequency as a genetic marker To the Editors: In spite of the rapid pace of development of molecular technology and expansion of genome sequence information, schizophrenia (SCH) related genes have remained elusive, partly because of the use of inefficacious markers of qualitative genetic characteristics in previous studies. Another cause may be that although genetic liability results from the combined effects of multiple genes rather than the effect of a single gene, genetic screening tests for SCH have rarely targeted multiple SCH-related genes. To overcome these shortcomings, we considered multiple SCH-related genes as an integer for the screening of new, highly efficacious markers of quantitative genetic characteristics. DNA samples were collected from 150 SCH patients (78 men and 72 women; mean age, 28.978.9 years) and 200 healthy subjects (100 men and 100 women; mean age, 3876.2 years) in Dalian, China. The alleles at nine randomly selected Combined DNA Index System (CODIS) short tandem repeat (STR) loci, CODIS STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820), were determined using the AmpFLSTR Profiler plus PCR Amplification Kit and detailed information was recorded in literature for these loci (Deng et al., 2007; Hui et al., 2014). They were chosen in this study because of reliable assay and rich data source. The combined allele frequency (CAF) was defined as the probability of two alleles being located together at a single locus in an individual. Frequently combined alleles are considered conservative alleles, whereas infrequently combined alleles are considered mutable alleles. Thus, CAF can be considered as a continuous variable from conservation to mutation, and a quantitative genetic marker. CAF was calculated as follows: For heterozygotes,
the CAF for each locus as the independent variable. The results revealed that the CAFs of FGA, D21S11, D5S818 and D7S820 produced statistically significant regression equation (po0.05); D3S1358, D8S1179, vWA, D13S317 and D18S51 were removed from regression equation. The logistic regression equation was as follows: Y ¼ 0:327 0:086CAF FGA þ 0:115CAF D21S11 0:057CAF D5S818 0:044CAF D7S820 Probability value ¼ expðyÞ=½1 þ expðyÞ The probability value from the logistic regression could be considered a genetic marker and the quantitative genetic characteristic was observed in the SCH group and the normal population using ROC analysis. The area under the curve (AUC) was 0.663 (po0.0001). All analyses were performed using the SPSS 13.0 statistical software package. By using CAF as a quantitative genetic marker instead of a count marker (allele frequency), the efficacy of genetic analysis can be improved. This study demonstrates that at least four of the nine randomly selected CODIS STR loci were related to SCH, indicating that many SCH-associated genes may exist in the genome, and it may be difficult or impossible to identify all SCH-associated genes. The analysis of CAFs via our method may exemplify a different approach to estimate the quantitative genetic characteristics of SCH and provide a more efficient and reliable model to determine the genetic predispositions of an individual to these disorders with using studies of the Psychiatric Genomics Consortium. References Deng, YJ., Yan, JW., Yu, XG., Li, YZ., Mu, HF., Huang, YQ., Shi, XT., Sun, WM., 2007. Genetic analysis of 15 STR loci in Chinese Han population from West China. Genomics Proteomics Bioinformatics 5 (1), 66–69. Hui, L., Liping, G., Jian, Y., Laisui, Y., 2014. A new design without control population for identification of gastric cancer-related allele combinations based on interaction of genes. Gene 540, 32–36.
CAF ¼ 2 ðfrequency of allele 1 frequency of allele 2Þ 100 Yang Guang, Zhang Lei, Xiao Nan, Liu Hui n College of Medical Laboratory, Dalian Medical University, Dalian 116044, China E-mail addresses: [email protected], [email protected] (L. Hui)
For homozygotes, CAF ¼ ðfrequency of alleleÞ2 100 The above allele frequencies are expected to be present in a normal population. The allele frequencies for the nine loci in our study were previously determined in a population (n¼ 7636) from the same geographic region from which our study subjects were recruited (Deng et al., 2007). A more important aspect of CAF is the reduction of allele dimension; with CAF, only one variable can be used to describe the characteristic of a locus; thus, CAFs from many loci can be considered as an integer to directly use in multivariate analysis tools. In this study, the binary logistic regression analysis (backward method) was performed, with SCH (1) and control (0) as the dependent variables and http://dx.doi.org/10.1016/j.psychres.2014.08.038 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Xie Soufu, Xv Junting Dalian Seventh Hospital, Dalian 116000, China Received 11 May 2014 18 August 2014 20 August 2014
n
Corresponding author.
