TY - JOUR
T1 - P < 5 × 10-8 has emerged as a standard of statistical significance for genome-wide association studies
AU - Jannot, Anne Sophie
AU - Ehret, Georg
AU - Perneger, Thomas
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Abstract Objectives In genome-wide association studies (GWASs), the practice regarding the choice of thresholds of significance and of thresholds used to include single nucleotide polymorphisms (SNPs) in a further validation stage is not well known. Here, we performed a systematic analysis of all GWASs published in two recent but nonconsecutive periods to assess whether any consensus was emerging regarding the choice of these thresholds. Study Design and Setting We identified 167 GWASs published during the first semester of 2011 and 105 published in the third trimester of 2012 and retrieved the genome-wide threshold of significance and the thresholds to include SNPs in a replication stage if applicable. Results The proportion of studies using 5 × 10-8 as a genome-wide significance threshold increased between 2011 and 2012 (40% vs. 64%, P < 0.001), whereas the proportion of articles that gave a justification for this threshold decreased. The distribution of thresholds used to include SNPs in the replication stage remained stable over time (median 10-5), and the variance remained large [interquartile range (10-6, 10-4)]. Conclusion Although 5 × 10-8 has become the de facto standard genome-wide threshold, practice regarding the choice of inclusion threshold for the replication step remains heterogeneous and did not ensure the best trade-off between power and type 1 error.
AB - Abstract Objectives In genome-wide association studies (GWASs), the practice regarding the choice of thresholds of significance and of thresholds used to include single nucleotide polymorphisms (SNPs) in a further validation stage is not well known. Here, we performed a systematic analysis of all GWASs published in two recent but nonconsecutive periods to assess whether any consensus was emerging regarding the choice of these thresholds. Study Design and Setting We identified 167 GWASs published during the first semester of 2011 and 105 published in the third trimester of 2012 and retrieved the genome-wide threshold of significance and the thresholds to include SNPs in a replication stage if applicable. Results The proportion of studies using 5 × 10-8 as a genome-wide significance threshold increased between 2011 and 2012 (40% vs. 64%, P < 0.001), whereas the proportion of articles that gave a justification for this threshold decreased. The distribution of thresholds used to include SNPs in the replication stage remained stable over time (median 10-5), and the variance remained large [interquartile range (10-6, 10-4)]. Conclusion Although 5 × 10-8 has become the de facto standard genome-wide threshold, practice regarding the choice of inclusion threshold for the replication step remains heterogeneous and did not ensure the best trade-off between power and type 1 error.
KW - Evaluation studies as topic
KW - False discovery rate
KW - Genome-wide association study
KW - Multiple testing
KW - Significance thresholds
KW - Validation studies
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U2 - 10.1016/j.jclinepi.2015.01.001
DO - 10.1016/j.jclinepi.2015.01.001
M3 - Article
C2 - 25666886
AN - SCOPUS:84925350670
SN - 0895-4356
VL - 68
SP - 460
EP - 465
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
IS - 4
M1 - 8783
ER -