Numerous epidemiological studies have shown that low birth weight is associated with diseases in adult life including type 2 diabetes, obesity, cardiovascular disease and the Metabolic Syndrome. If so, attempts to understand its etiology as well as the patterns underlying its association with diseases in adulthood would be of utmost importance especially in populations such as the Mexican Americans, which are prone to diseases such as obesity, type 2 diabetes and the Metabolic Syndrome. Knowledge about the genetic basis of variation in birth weight is very limited. Also, little is known about whether associations between birth weight and diseases in adult life have any common genetic determinants. The purpose of this project is to conduct a genetic epidemiologic investigation involving molecular genetic data, birth weight data and its related adult phenotypic data, and statistical genetic techniques to examine the genetic basis of variation in birth weight in 210 Mexican American families that are currently under investigation in relation to the genetic determination of various diseases including obesity, type 2 diabetes, and hypertension. Specifically, using variance-components linkage techniques, this study aims to map susceptibility genes for birth weight. The main objectives of our proposal are: 1) to collect birth weight data for about 700 individuals in addition to the birth weight data we have already collected for 602 individuals; 2) to identify potential susceptibility loci for birth weight using multipoint linkage approach; 3) to further explore the regions of interest by typing additional markers in each region of interest and using multipoint linkage analysis; 4) to examine whether these susceptibility loci have any pleiotropic influences on adult diseases and metabolic disorders; and 5) to identify multiple loci affecting birth weight and to examine interactional effects of genes influencing birth weight. Using birth weight data from about 800 individuals (110 families) on whom a 10cM genome scan map is available, we will conduct a multi-point linkage analysis to identify susceptibility loci for birth weight. After detecting potential signals for linkage, we will perform additional genotyping with 10 markers per region using data from about 1300 individuals to precisely localize the susceptibility genes for birth weight using the multipoint approach. We will also examine whether the loci for birth weight have any common genetic influences(i.e., pleitropy) on diseases in adulthood such as obesity, type 2 diseases, hypertension, and the Metabolic Syndrome. Given that we have already localized various loci across the genome affecting such traits as type 2 diabetes, obesity, insulin resistance, and lipids, this present study will provide a unique opportunity to identify genes that have common genetic influences on birth weight and metabolic diseases in adulthood.
