title: Cohen's h for detection of disease association with rare genetic variants.
abstract: BACKGROUND
  The power of the genome wide association studies starts to go down when the minor allele frequency (MAF) is below 0.05. Here, we proposed the use of Cohen's h in detecting disease associated rare variants. The variance stabilizing effect based on the arcsine square root transformation of MAFs to generate Cohen's h contributed to the statistical power for rare variants analysis. We re-analyzed published datasets, one microarray and one sequencing based, and used simulation to compare the performance of Cohen's h with the risk difference (RD) and odds ratio (OR).
  
  
  RESULTS
  The analysis showed that the type 1 error rate of Cohen's h was as expected and Cohen's h and RD were both less biased and had higher power than OR. The advantage of Cohen's h was more obvious when MAF was less than 0.01.
  
  
  CONCLUSIONS
  Cohen's h can increase the power to find genetic association of rare variants and diseases, especially when MAF is less than 0.01.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Wen
authors.affiliation: Department of Molecular Biology and Human Genetics, Tzu-Chi University, 701, Sec 3, Chung-Yang Rd, Hualien 97004, Taiwan. jihiyeh@gms.tcu.edu.tw.
authors.forename: Jih-I
authors.initials: JI
authors.lastname: Yeh
mesh_terms: D000465:Algorithms; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide