Segregation Analysis Of Body Mass Index In Chinese And Hardy-Weinberg Disequilibrium Mapping For Quantitative Trait Locus

Complex segregation analysis is designed to detect major genes underlying complex phenotypes and is a general method for evaluating the transmission of a trait within pedigrees. It proceeds by testing models of varying degrees of generality, both to determine whether a Mendelian locus is likely to exert a large effect on the phenotype of interest and to estimate the magnitude of genetic sources of variation in the trait. This information is valuable both as a prelude to linkage analysis, which generally assumes Mendelian transmission. Class A regressive model of quantitative trait assumes that sib-sib residual correlations are equal and determined by the parent-offspring correlation, Class D regressive model assumes that the sibling correlations are equal, but not necessarily due to common parentage alone. Body mass index (defined as the ratio of weight to height2 in units of kilograms/meters2) is an important indictor of obesity (obesity is defined as having body .mass index >30). Several studies have reported evidence for major genes for body mass index among different populations. However, no such studies have been performed to examine the inheritance of body mass index in Chinese. In the present study, the purposes are to determine the heritability of body mass index, and examine the mode of inheritance of body mass index variation in Chinese. We performed familial correlation and complex segregation analyses (Class D regressive model) for body mass index in a Chinese sample composed of 401 nuclear families, with 1, 260 total individuals. All subjects belong to the Han ethnic group and were collected randomly from the local population of Shanghai City. Before the genetic analyses, the data were examined for dependence on age and sex. The data wereadjusted for age due to the fact that age is potentially significantly correlated with body mass index. The obtained results do not support a major gene for body mass index in Chinese, the discrepancies between our study and previous studies may result from ethnic difference between Chinese and other populations; The general model provides the best fit to the data, while the environmental model is the second parsimonious model, perhaps due to complex mode of Body mass index inheritance; A moderate heritability estimate is found for body mass index (h2=0.313), lower than that of other populations, this is presumably due to the fact that aside from the influence of genetic bases, body mass index is strongly influenced by environmental factors and that there is a low proportion of obese individuals in samples (only 4. 1% individuals have body mass index >30). Considering that Body mass index is a complex trait affected by especially sex and age, again, segregation analysis was undertaken in this study, age effects directly incorporated into the genetic model. The result showed that the general model provides the best fit to the data. However, the codominant fashion is the second parsimonious model. It is suggested that identification of specific genes for body mass index in Chinese, at least within the same data set, is a serious challenge because of lack of evidence of a major gene for body mass index in our Chinese sample.Fine mapping of a quantitative trait locus can be accomplished on the basis of deviations from Hardy-Weinberg equilibrium at closely linked marker loci. Earlier Hardy-Weinberg disequilibrium (HWD) measures may introduce bias in the fine mapping because they are dependent on marker allele frequencies across loci. We developed four new HWD indices that do not depend on marker allele frequencies. Two are for use when marker allelefrequencies in a study population are known, and two ( LCD} are for use when marker allele frequencies in a study population are not known and are only known in the extreme samples. The new measures are a function of the genetic distance between the marker locus and a QTL. Through simulations, we found that when marker allele frequencies vary across loci, the previous HWD measures are biased and not powe...