Parental Consanguinity Among Schizophrenia Patients Living In A Rural Community Of South India
About the Practice
The research on association of consanguinity with schizophrenia is a relatively novel one and needs replication in different settings. Finding an association between consanguinity and a higher risk of developing schizophrenia could suggest a role of recessive genes which might be playing an important role in the susceptibility to schizophrenia. Genetic effects of inbreeding can be traced to the fact that the inbred individual may carry two copies of a gene that was present in a single copy in the common ancestor of his/her consanguineous parents. Since inbreeding increases the chance of inheriting identical alleles at loci, it can also increase the risk of inheriting two identical copies of particular risk alleles at each locus and thus increase the risk of schizophrenia. Among highly consanguineous populations, little has been published on the effects of consanguinity on the complex late-onset disorders that account for most of the public health burden. Although our understanding of the genetic basis for schizophrenia has increased substantially, the precise mechanism of inheritance still remains obscure. Very few studies have taken into account the consanguineous vulnerability associated with major psychotic disorders especially those with pronounced disability features. Also, the consanguinity studies are highly localized and many areas (States) are yet to be explored fully. Most of the earlier such studies are based on self report. The study therefore aims to access parental consanguinity among the patients and healthy controls living in a rural south Indian community using more advanced molecular genetics technology.
Detail:
Emerging evidence indicate that consanguineous marriages are a risk factor for schizophrenia. Systematic finding of parental consanguinity being linked to differential risk for developing schizophrenia are very less and replicating the study in a different socio-cultural setting is much needed for consideration of parental consanguinity as a significant contributor for schizophrenia. We attempted to provide insights into the differential effect of the parental consanguinity on susceptibility to schizophrenia. Rural communities in South India, where consanguineous marriages are fairly common, are well suited for this study. In this study we examined the issue of degree of parental consanguinity among patients with schizophrenia and healthy control subjects living in a rural community of South India (Cases, n = 120; Controls, n = 222). We used clinical interview method (‘self report’) along with Dbased rates for assessing parental consanguinity in order to add substantial reliability to our data. Dbased rates are more reportedly more precise and are relatively a new concept. The clinical interview method helped in ascertaining the consanguinity pattern of parental marriage by drawing family pedigrees (of three to five generations back). The information provided by the parents / relatives was crosschecked by different members of the family. A participant was considered to be consanguineous, if the parents shared a common ancestor no more remote than a great-great grandparent. This was followed by Danalysis using SNPs (n = 384) (‘DNA-based’ rates) and calculating individual coefficients of inbreeding ‘f’, to assess parental consanguinity. Parental consanguinity was defined as coefficient of inbreeding ‘f’ >= 0.0156. This arbitrary limit has been chosen because the genetic influence in marriages between couples related to a lesser degree would usually be expected to differ only slightly from that observed in the general population. Self reported parental consanguinity was not significantly elevated among the patients (Cases: 10.71%, controls: 7.25%; χ2 = 0.493, p = 0.4825, 1 df). Shapiro-Wilk’s statistics showed that while the distribution was normal among cases (statistic: 0.994; df =120; p=0.884), the distribution was significantly deviant from normal distribution among controls (statistic=0.979; df=222; p=0.003). Hence, we conducted Mann-Whitney U test to compare ‘f’ values in these groups (Table – 9). Mean ranks for cases and controls were respectively 188.2 and 162.47 and the difference was statistically significant (p=0.022). In other words, Coefficients of Inbreeding ‘f’ was significantly higher among cases than controls. We had a-priori proposed cut-off of f >0.0156 as an indicator of parental consanguinity. With this cut-off, 75 of 120 cases (62.5%) and 108 of 222 controls (48.6%) had parental consanguinity. This difference was statistically significant: χ2 =6.008; df=1; p=0.014, with an odds-ratio of 1.75 (95% CI=1.118 – 2.769). Cases were 1.75 times more likely to have parental consanguinity than the controls. We thoroughly evaluated the relative performance of the clinical interview versus Dbased measures of parental consanguinity in this study population. We did not find a difference between the cases and controls in terms of parental consanguinity assessed by clinical interview method. By this method the rates of parental consanguinity elicited in either group was much smaller than the ones inferred through Dbased method. It is possible that this discrepancy is in part related to inability of the family member to recall the details of the nature of the marriages precisely. Our data suggest that schizophrenia is associated with higher parental consanguinity. This was found in results in which the degree of parental consanguinity was considered as a continuous variable as well as when the same was considered as a categorical variable. The result was consistent across different degree of quality control; both in terms of SNP call rates as well as Hardy Weinberg’s Equilibrium. Larger cross-sectional studies are warranted to validate our findings.
About the Innovator
Address: vikasagarwal1985@gmail.com
City: Thirthalli
State: Karnataka
PIN Code 560029
Email: vikasagarwal1985@gmail.com
Contact No: 9538228105.0
Practice Details
Link: Many new technologies for SNP genotyping have been developed in the last few years, such as GeneChip array, the Bead array etc which has provided ultra multiplex and high-throughput genotyping but are not cost effective for genotyping a large number of samples for a modest number of SNPs (few hundreds of SNPs). Hence to meet our needs of medium multiplex high throughput SNP genotyping for 384 SNPs we used a nanofluidic platform. Using Fluidigm® SNP Type™ assays we achieved call rates of greater than 95 % and call accuracy of greater than 98 %. It involved comparatively lower cost and minimum experimental setup time.
Problem Scale: Worldwide