Genome-wide Association in Families: Data Integrity, Design and Methods Issue

描述（由申请人提供）：广泛的全基因组单核苷酸多态性（snp）现在是可用的。理论上，我们可以系统地考虑基因组的所有区域，以确定与疾病易感性或不利风险因素相关的区域。然而，在我们能够在全基因组关联研究中实际使用所有遗传信息之前，重要的问题需要得到解决。需要开发方法来检测和解决基因分型错误，我们需要专门为家庭数据设计的新的分析策略，以解释多重比较。

DESCRIPTION (provided by applicant): Extensive genome-wide single nucleotide polymorphisms (SNPs) are now available. Theoretically, we can systematically consider all the regions of the genome to identify those regions associated with disease susceptibility or unfavorable risk factors. Important issues need to be resolved however, before we can practically use all the genetic information in genome-wide association studies. Methods need to be developed to detect and resolve genotyping errors and we need new, analytical strategies designed specifically for family data that will account for multiple comparisons. Many large family-based studies, including our own, were initiated with the goal of first detecting linkage to identify chromosomal regions likely to harbor mutations having relatively large effects on important risk factors for heart disease. One of our studies, the Heritability and Phenotype Intervention (HAPI) Heart Study, includes extensive coronary heart disease risk factor data and 500,000 SNPs on 900 adults in Old Order Amish pedigrees. Our families are very suitable for genome-wide association studies and they offer special opportunities, compared to population-based samples, because families provide a direct test of allelic transmissions. This application addresses two specific issues pertaining to genome-wide association studies in families. One relates to development, implementation, testing, and dissemination of efficient ways to clean and process genome-wide SNP data and then create haplotypes. The other relates to developing analytic strategies that combine information from population- and transmission-based association tests to improve power, minimize false positive rates, and enhance efficiency for detecting SNP-trait associations.