Avoiding the high Bonferroni penalty in genome-wide association studies.
paper
Cited
Public
Unavailable
- Authors
- Gao, Xiaoyi; Becker, Lewis C; Becker, Diane M; Starmer, Joshua D; Province, Michael A
- Year
- 2010
- Journal
- Genetic epidemiology
- PMID
- 19434714
- DOI
- 10.1002/gepi.20430
- PMCID
- PMC2796708
A major challenge in genome-wide association studies (GWASs) is to derive the multiple testing threshold when hypothesis tests are conducted using a large number of single nucleotide polymorphisms. Permutation tests are considered the gold standard in multiple testing adjustment in genetic association studies. However, it is computationally intensive, especially for GWASs, and can be impractical if a large number of random shuffles are used to ensure accuracy. Many researchers have developed approximation algorithms to relieve the computing burden imposed by permutation. One particularly attractive alternative to permutation is to calculate the effective number of independent tests, M(eff), which has been shown to be promising in genetic association studies. In this study, we compare recently developed M(eff) methods and validate them by the permutation test with 10,000 random shuffles using two real GWAS data sets: an Illumina 1M BeadChip and an Affymetrix GeneChip Human Mapping 500K Array Set. Our results show that the simpleM method produces the best approximation of the permutation threshold, and it does so in the shortest amount of time. We also show that M(eff) is indeed valid on a genome-wide scale in these data sets based on statistical theory and significance tests. The significance thresholds derived can provide practical guidelines for other studies using similar population samples and genotyping platforms.
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| Association of milk protein genes with fertilization rate and early embryonic development in Holstein dairy cattle. | PeΓ±agaricano F et al. | β | 2012 | β |
| Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. | Jahanshad N et al. | β | 2012 | β |
| Detecting rare variant associations by identity-by-descent mapping in case-control studies. | Browning SR et al. | β | 2012 | β |
| DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME. | Jahanshad N et al. | β | 2012 | β |
| Genetic heterogeneity according to age at onset in bipolar disorder: a combined positional cloning and candidate gene approach. | Dizier MH et al. | β | 2012 | β |
| Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions. | Pinel P et al. | β | 2012 | β |
| Genome-wide association study identifies candidate markers for bull fertility in Holstein dairy cattle. | PeΓ±agaricano F et al. | β | 2012 | β |
| Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. | Mead S et al. | β | 2012 | β |
| GWA analysis for milk production traits in dairy sheep and genetic support for a QTN influencing milk protein percentage in the LALBA gene. | GarcΓa-GΓ‘mez E et al. | β | 2012 | β |
| Molecular genetic studies of complex phenotypes. | Marian AJ | β | 2012 | β |
| Proteomic characterization of histotroph during the preimplantation phase of the estrous cycle in cattle. | Mullen MP et al. | β | 2012 | β |
| An evolutionary genomic approach to identify genes involved in human birth timing. | Plunkett J et al. | β | 2011 | β |
| A new approach to account for the correlations among single nucleotide polymorphisms in genome: wide association studies. | Chen Z et al. | β | 2011 | β |
| Differential susceptibility to adolescent externalizing trajectories: examining the interplay between CHRM2 and peer group antisocial behavior. | Latendresse SJ et al. | β | 2011 | β |
| Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search. | Stein JL et al. | β | 2011 | β |
| DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (GsΞ±)-encoding (GNAS) genomic imprinting domain are associated with performance traits. | Sikora KM et al. | β | 2011 | β |
| Factors affecting the effective number of tests in genetic association studies: a comparative study of three PCA-based methods. | Wen SH et al. | β | 2011 | β |
| Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. | Hamza TH et al. | β | 2011 | β |
| Impact of a functional KIR2DS4 allele on heterosexual HIV-1 transmission among discordant Zambian couples. | Merino A et al. | β | 2011 | β |
| Molecular Genetics and Economics. | Beauchamp JP et al. | β | 2011 | β |
| Multiple testing corrections for imputed SNPs. | Gao X | β | 2011 | β |
| Novel association analysis between 9 short tandem repeat loci polymorphisms and coronary heart disease based on a cross-validation design. | Hui L et al. | β | 2011 | β |
| Novel rank-based approaches for discovery and replication in genome-wide association studies. | Kuo CL et al. | β | 2011 | β |
| Significance levels in genome-wide interaction analysis (GWIA). | Becker T et al. | β | 2011 | β |
| Accounting for multiple comparisons in a genome-wide association study (GWAS). | Johnson RC et al. | β | 2010 | β |
| A genome-wide association study of carotid atherosclerosis in HIV-infected men. | Shrestha S et al. | β | 2010 | β |
| Detection of quantitative trait loci affecting the milk fatty acid profile on sheep chromosome 22: role of the stearoyl-CoA desaturase gene in Spanish Churra sheep. | GarcΓa-FernΓ‘ndez M et al. | β | 2010 | β |
| DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle. | Magee DA et al. | β | 2010 | β |
| Genetics of human social behavior. | Ebstein RP et al. | β | 2010 | β |
| PERMORY: an LD-exploiting permutation test algorithm for powerful genome-wide association testing. | Pahl R et al. | β | 2010 | β |
| Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth. | Plunkett J et al. | β | 2010 | β |
| Replication of previous genome-wide association studies of bone mineral density in premenopausal American women. | Ichikawa S et al. | β | 2010 | β |
| The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm. | Deka R et al. | β | 2010 | β |
| Voxelwise genome-wide association study (vGWAS). | Stein JL et al. | β | 2010 | β |
| Serotonin transporter gene, depressive symptoms, and interleukin-6. | Su S et al. | β | 2009 | β |
| The null distributions of test statistics in genomewide association studies. | Chen X et al. | β | 2009 | β |
| The role of copy number variation in susceptibility to amyotrophic lateral sclerosis: genome-wide association study and comparison with published loci. | Wain LV et al. | β | 2009 | β |