Testing Allele Transmission of a SNP-Set using a Family-based Generalized Genetic Random Field Method

Details

• Alternative Title:
  Genet Epidemiol
• Personal Author:
  Li, Ming ; Li, Jingyun ; He, Zihuai ; Lu, Qing ; Witte, John S ; Macleod, Stewart L. ; Hobbs, Charlotte A. ; Cleves, Mario A.
• Corporate Authors:
  National Birth Defect Prevention Study
• Description:
  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).
• Subjects:
  Allele Distortion Alleles Article Case-Control Studies Congenital Heart Defects Family Family-based Association Test Generalized Genetic Random Field Genetic Association Studies Genetic Similarity Genotype Heart Defects, Congenital Humans Models, Genetic Phenotype Polymorphism, Single Nucleotide Population Stratification

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• Source:
  Genet Epidemiol. 40(4):341-351
• Pubmed ID:
  27061818
• Pubmed Central ID:
  PMC5061344
• Document Type:
  Journal Article
• Funding:
  UL1 TR000039/TR/NCATS NIH HHS/United States ; U01 DD000491/DD/NCBDD CDC HHS/United States ; UL1TR000039/TR/NCATS NIH HHS/United States ; R03 DE022379/DE/NIDCR NIH HHS/United States ; 5U01DD000491/DD/NCBDD CDC HHS/United States ; KL2 TR000063/TR/NCATS NIH HHS/United States ; 5R01HD039054/HD/NICHD NIH HHS/United States ; KL2TR000063/TR/NCATS NIH HHS/United States ; UL1 TR001108/TR/NCATS NIH HHS/United States ; U01 DD001039/DD/NCBDD CDC HHS/United States ; K01 DA033346/DA/NIDA NIH HHS/United States ; R01 HD039054/HD/NICHD NIH HHS/United States
• Volume:
  40
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0f90d4611557afd3ebbab389c63459d7945dcc5fe12364cdda21713cdd8d62d6
• Download URL:
  https://stacks.cdc.gov/view/cdc/41725/cdc_41725_DS1.pdf
• File Type:
  [PDF - 4.22 MB ]