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Evaluation of Nyholt's procedure for multiple testing correction.

Daria Salyakina1, Shaun R Seaman, Brian L Browning

  • 1Max-Planck Institute of Psychiatry, Munich, Germany. daria@mpipsykl.mpg.de

Human Heredity
|August 25, 2005
PubMed
Summary
This summary is machine-generated.

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Nyholt's method for multiple testing in SNP association studies is not reliable. Its type I error rate varies and can be overly conservative, making permutation tests a better choice.

Area of Science:

  • Genetics
  • Statistical Genetics
  • Bioinformatics

Background:

  • Multiple testing is a challenge in SNP association studies.
  • Nyholt's method offers an efficient approach by estimating an 'effective number' of independent tests.
  • The performance of Nyholt's method requires thorough empirical and theoretical evaluation.

Purpose of the Study:

  • To empirically and theoretically evaluate Nyholt's method for multiple testing in SNP association studies.
  • To assess the accuracy and reliability of Nyholt's method under various genetic scenarios.

Main Methods:

  • Applied Nyholt's method to 291 SNPs across 31 genes.
  • Utilized permutation testing to determine type-I error rates.
  • Algebraically investigated the effective number of independent tests considering haplotype block structure.

Related Experiment Videos

Main Results:

  • The nominal 5% type I error rate fluctuated between under 3% and over 7%, influenced by linkage disequilibrium.
  • Theoretical analysis indicated the method can be overly conservative with haplotype block structures.

Conclusions:

  • Nyholt's method may serve as an exploratory tool but is not a sufficient replacement for permutation tests.
  • Permutation tests remain the gold standard for accurate multiple testing adjustments in SNP association studies.