Registro de gemelosutilidades, organización y supuestos clave. Registro de gemelos de Murcia.

Abstract

This doctoral dissertation deals with twin registries and the "Murcia Twin Registry" (MTR) in particular, as a fundamental research resource for in depth understanding of the relative contribution of genetic and environmental factors to behavior. Genetically informative designs, specifically twin studies, are an important resource for the analysis of the causes of human phenotypic variation. These designs are the methodology of choice in order to separate genetic from environmental causes in family resemblance. Currently, such studies are widely implemented and entail a high degree of specialization, in accordance with its enormous research potential. Their development is based on the existence of multiple births records. Nowadays, twin registries are distributed worldwide, and their implantation represent a methodological response to specific twin studies initiated by the scientific community. Zygosity determination, assessment of the equal environment assumption (EEA), and verification of the representativeness of the sample, are core issues of the twin studies methodology. These three elements are the key to ensure the usefulness of the comparisons, and the validity of the results obtained. It therefore seems clear that testing these three questions is an essential principle in establishing the scientific utility of any twin registry. This dissertation has three main objectives: to validate the zygosity questionnaire used so far in the MTR, by means of comparing the classification by this instrument and the zygosity results obtained by genetic markers; to analyze the accuracy of the equal environments assumption among participants of the MTR, comparing the data about periods of shared residence between MZ and DZ twins; and to investigate to what extent the sample of subjects participating in the MTR is representative of the reference population, according to geographical context, sex and age group. The design for the overall development of the MTR is a population-based cohort, consisting of individuals born from multiple births and living in the Region of Murcia. These subjects are included in a twin registry with voluntary participation. This particular work uses the full sample of MTR participants, as well as some selected sub-samples, depending on the specific objectives of each of the investigations that compose it. In the same way, the procedures used vary and adapt to the specific objectives of analysis. The main conclusion of this dissertation is that the general objective of validating the MTR as a research resource has been reasonably achieved. Some of the main findings that contribute to that objective can be highlighted. The validity of the Spanish adaptation of the zygosity questionnaire has been proved. There is a major discrepancy between the subjective zygosity classification of the twins, and the classification by questionnaire and analysis of genetic markers, showing a striking overestimation of dizygosity. The proportion of twins living in the same or different municipality throughout their lives is not influenced by the type of zygosity, fulfilling in general, and a priori, the equal environment assumption. What is more, zygosity is not related to the proportion of pairs who have lived in the same town during the first 16 years of life. Finally, the representativeness of the sample of the MTR in relation to the reference populations of Murcia and Spain has been estimated and the results support the generalizability of the data to the general population.