Chung Ren-Hua, Kinnamon Daniel D, Martin Eden R
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Newyork, Taiwan.
Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Methods Mol Biol. 2017;1666:391-407. doi: 10.1007/978-1-4939-7274-6_19.
Family-based designs have been commonly used in association studies. Different family structures such as extended pedigrees and nuclear families, including parent-offspring triads and families with multiple affected siblings (multiplex families), can be ascertained for family-based association analysis. Flexible association tests that can accommodate different family structures have been proposed. The pedigree disequilibrium test (PDT) (Martin et al., Am J Hum Genet 67:146-154, 2000) can use full genotype information from general (possibly extended) pedigrees with one or multiple affected siblings but requires parental genotypes or genotypes of unaffected siblings. On the other hand, the association in the presence of linkage (APL) test (Martin et al., Am J Hum Genet 73:1016-1026, 2003) is restricted to nuclear families with one or more affected siblings but can infer missing parental genotypes properly by accounting for identity-by-descent (IBD) parameters. Both the PDT and APL test are powerful association tests in the presence of linkage and can be used as complementary tools for association analysis. This chapter introduces these two tests and compares their properties. Recommendations and notes for performing the tests in practice are provided.
基于家系的设计已普遍用于关联研究。不同的家庭结构，如扩展家系和核心家庭，包括亲代-子代三联体以及有多个患病同胞的家庭（多重家庭），都可用于基于家系的关联分析。人们已经提出了能够适应不同家庭结构的灵活关联检验方法。系谱不平衡检验（PDT）（Martin等人，《美国人类遗传学杂志》67:146 - 154，2000年）可以利用来自有一个或多个患病同胞的一般（可能是扩展的）系谱的完整基因型信息，但需要亲代基因型或未患病同胞的基因型。另一方面，连锁存在时的关联（APL）检验（Martin等人，《美国人类遗传学杂志》73:1016 - 1026，2003年）仅限于有一个或多个患病同胞的核心家庭，但通过考虑同源等位基因（IBD）参数能够正确推断缺失的亲代基因型。在存在连锁的情况下，PDT和APL检验都是强大的关联检验方法，并且可以用作关联分析的互补工具。本章介绍这两种检验方法并比较它们的特性。还提供了在实际操作中进行这些检验的建议和注意事项。
