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Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.

Norlelawati AT, Kartini A, Norsidah K, Ramli M, Tariq AR, Wan Rohani WT - Psychiatry Investig (2015)

Bottom Line: The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)].This is similar to the meta-analysis findings for the Caucasian populations.However, the finding of the study is limited due to possible genetic stratification and the small sample size.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University, Pahang, Malaysia.

ABSTRACT

Objective: Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)].

Methods: We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods.

Results: In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations.

Conclusion: The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size.

No MeSH data available.


Related in: MedlinePlus

Lingkage disequilibrium between the SNPs selected in the DISC1 gene constructed using Haploview 4.2 of HCB Chr 1: 229329..230397k database. The rs4658971, rs843979 and rs821616 were uncaptured. Values are equal to D' multiplied by 100 (Values are not shown for D'=1). SNP: single nucleotid polymorphism.
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Figure 1: Lingkage disequilibrium between the SNPs selected in the DISC1 gene constructed using Haploview 4.2 of HCB Chr 1: 229329..230397k database. The rs4658971, rs843979 and rs821616 were uncaptured. Values are equal to D' multiplied by 100 (Values are not shown for D'=1). SNP: single nucleotid polymorphism.

Mentions: Peripheral blood samples were collected from all 575 subjects. Genomic DNA was extracted using a Gentra® Puregene® (Qiagen, Germany) purification kit, following the manufacturer's protocol. Four SNPs (rs821597, rs4658971, rs843979, and rs821616) that were located in the region between Intron 10 and Exon 11 of DISC1 were selected based on a previous study that was conducted on Han Chinese subjects.17 Another six SNPs (rs1538979, rs2812385, rs4658890, rs1407599, rs16854957, and rs2038636) were selected based on the meta-analysis findings of DISC1 studies performed among Caucasians in Europe.2 The last SNP, rs2509382, which was located at 11q14.3, represented the mutual translocation region of the famously translocated DISC1 (1q42.1) gene.21 The intermarker linkage disequilibrium patterns of the SNPs are shown in Figure 1.


Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.

Norlelawati AT, Kartini A, Norsidah K, Ramli M, Tariq AR, Wan Rohani WT - Psychiatry Investig (2015)

Lingkage disequilibrium between the SNPs selected in the DISC1 gene constructed using Haploview 4.2 of HCB Chr 1: 229329..230397k database. The rs4658971, rs843979 and rs821616 were uncaptured. Values are equal to D' multiplied by 100 (Values are not shown for D'=1). SNP: single nucleotid polymorphism.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310907&req=5

Figure 1: Lingkage disequilibrium between the SNPs selected in the DISC1 gene constructed using Haploview 4.2 of HCB Chr 1: 229329..230397k database. The rs4658971, rs843979 and rs821616 were uncaptured. Values are equal to D' multiplied by 100 (Values are not shown for D'=1). SNP: single nucleotid polymorphism.
Mentions: Peripheral blood samples were collected from all 575 subjects. Genomic DNA was extracted using a Gentra® Puregene® (Qiagen, Germany) purification kit, following the manufacturer's protocol. Four SNPs (rs821597, rs4658971, rs843979, and rs821616) that were located in the region between Intron 10 and Exon 11 of DISC1 were selected based on a previous study that was conducted on Han Chinese subjects.17 Another six SNPs (rs1538979, rs2812385, rs4658890, rs1407599, rs16854957, and rs2038636) were selected based on the meta-analysis findings of DISC1 studies performed among Caucasians in Europe.2 The last SNP, rs2509382, which was located at 11q14.3, represented the mutual translocation region of the famously translocated DISC1 (1q42.1) gene.21 The intermarker linkage disequilibrium patterns of the SNPs are shown in Figure 1.

Bottom Line: The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)].This is similar to the meta-analysis findings for the Caucasian populations.However, the finding of the study is limited due to possible genetic stratification and the small sample size.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University, Pahang, Malaysia.

ABSTRACT

Objective: Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)].

Methods: We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods.

Results: In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations.

Conclusion: The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size.

No MeSH data available.


Related in: MedlinePlus