Date of Submission


Date of Award


Institute Name (Publisher)

Indian Statistical Institute

Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy

Subject Name



Human Genetics Unit (HGU-Kolkata)


Majumder, Partha Pratim (HGU-Kolkata; ISI)

Abstract (Summary of the Work)

The present study can be broadly classified in the area of genetic epidemiology, which is conventionally defined as a science that deals with the aetiology, distribution, and control of disease in groups of relatives and with inherited causes of disease in populations (Morton 1982, 1993). One of the major goals of genetic epidemiology is the study of the nature and extent of clustering of a disease in families and in defined ethnic groups. The study of a disorder within the genetic epidemiological framework is performed by testing :(1) whether the disorder clusters in families?(2) whether observed familiarity is caused by biology. Dally inherited susceptibility factors or environmental exposure or culturally inherited risk factors?(3) whether the genetic susceptibility factors are inherited in accordance with a specified model of inheritance?It may be emphasized that familial aggregation, though a necessary condition, is not a sufficient one to establish that a disorder is genetic. This is be- cause even a non-genetic, environmentally determined disorder can aggregate in families due to common familial environmental factors. However, testing for familial aggregation needs to be performed prior to any formal genetic analysis. Several tests of familial aggregation have been proposed in the literature (Chakraborty et al. 1980, 1984; Hill 1980; Thomson 1980; Majumder 1982). Among these, the more widely used ones are designed to test whether :a) prevalence of the disorder among relatives of an affected individual is higher than the prevalence among relatives of a normal individual (relative risk);b) prevalence of the disorder among relatives of an affected individual is higher than the general population prevalence. Standardized mortality ratio (SMR) is commonly used. If the SMR is significantly greater than unity, indicating familial aggregation, then to examine whether the observed aggregation is due to genetic factors, one proceeds to test whether affected members of a family are significantly 'closer' – in the sense of kinship coefficient (Hill 1980) or some other measure of biological distance (Chakraborty et al. 1980; Thomson 1980) than a pair of randomly chosen affected individuals from the population;c) age and gender specific correlation of the disorder between pairs of related affected individuals is significantly greater than zero (Chakraborty et al. 1984).For many chronic disorders, an individual with a higher genetic risk often has a lower age at onset. Thus, in a high-risk family one may not observe a significant increase in the number of affected individuals, but an aggregation of a few early-onset cases. To take this into account, Majumder (1982) and Chakraborty et al. (1984) devised a test procedure to detect familial aggregation, designed broadly to detect excess prevalence of a disorder in a family.If a disorder clusters in families more frequently than is expected by chance, then determining the reason for familial clustering can contribute both to the understanding of disease aetiology and to its control (King et al. 1984). There are three mechanisms that may explain familiarity :(1) a gene or genes increasing susceptibility to disease may be biologically inherited;


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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.


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