Linear mixed model has often been utilized for genetic association analysis with family-based samples. The correlation matrix for family-based samples is constructed with kinship coefficient and assumes that parental phenotypes are independent and the amount of correlations between parent and offspring is same as that of correlations between siblings. However, for instance, there are positive correlations between parental heights, which indicates that the assumption for correlation matrix is often violated. The statistical validity and power are affected by the appropriateness of assumed variance covariance matrix, and in this thesis, we provide the linear mixed model with flexible variance covariance matrix. Our results show that the proposed method is usually more efficient than existing approaches, and its application to genome-wide association study of body mass index illustrates the practical value in real data analysis.