Testing Allele Transmission of an SNP Set Using a Family-Based Generalized Genetic Random Field Method
| Autor: | Li, Ming, Li, Jingyun, He, Zihuai, Lu, Qing, Witte, John S, Macleod, Stewart L, Hobbs, Charlotte A, Cleves, Mario A, National Birth Defects Prevention Study |
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| Rok vydání: | 2016 |
| Předmět: |
Genotype
population stratification Epidemiology family-based association test Congenital Genetic Models National Birth Defects Prevention Study Genetics Humans 2.1 Biological and endogenous factors Family Polymorphism Aetiology Alleles Genetic Association Studies Heart Defects Pediatric generalized genetic random field Prevention Human Genome Single Nucleotide allele distortion congenital heart defects Phenotype Case-Control Studies Public Health and Health Services genetic similarity |
| Zdroj: | Genetic epidemiology, vol 40, iss 4 |
| Popis: | Family-based association studies are commonly used in genetic research because they can be robust to population stratification (PS). Recent advances in high-throughput genotyping technologies have produced a massive amount of genomic data in family-based studies. However, current family-based association tests are mainly focused on evaluating individual variants one at a time. In this article, we introduce a family-based generalized genetic random field (FB-GGRF) method to test the joint association between a set of autosomal SNPs (i.e., single-nucleotide polymorphisms) and disease phenotypes. The proposed method is a natural extension of a recently developed GGRF method for population-based case-control studies. It models offspring genotypes conditional on parental genotypes, and, thus, is robust to PS. Through simulations, we presented that under various disease scenarios the FB-GGRF has improved power over a commonly used family-based sequence kernel association test (FB-SKAT). Further, similar to GGRF, the proposed FB-GGRF method is asymptotically well-behaved, and does not require empirical adjustment of the type I error rates. We illustrate the proposed method using a study of congenital heart defects with family trios from the National Birth Defects Prevention Study (NBDPS). |
| Databáze: | OpenAIRE |
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