An empirical comparison of meta-analyses of published gene-disease associations versus consortium analyses.
OBJECTIVE
Consortia of investigators currently compile sufficiently large sample sizes to investigate the effects of low-risk susceptibility genetic variants. It is not clear how the results obtained by consortia compare with those derived from meta-analyses of published studies.


METHODS
We performed meta-analyses of published data for 16 genetic polymorphisms investigated by the Breast Cancer Association Consortium, and compared sample sizes, heterogeneity, and effect sizes. PubMed, Web of Science, and Human Genome Epidemiology Network databases were searched for breast cancer case-control association studies.


RESULTS
We found that meta-analyses of published data and consortium analyses were based on substantially different data. Published data by non-consortium teams amounted on average to 26.9% of all available data (range 3.0 -50.0%). Both approaches showed statistically significant decreased breast cancer risks for CASP8 D302H. The meta-analyses of published data demonstrated statistically significant results for five other genes and the consortium analyses for two other genes, but the strength of this evidence, evaluated on the basis of the Venice criteria, was not strong.


CONCLUSIONS
Because both approaches identified the same gene out of 16 candidates, the methods can be complimentary. The expense and complexity of consortium-based studies should be considered vis-à-vis the potential methodological limitations of synthesis of published studies.
Department of Public Health, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. a.janssens@erasmusmc.nl
A Cecile J W
AC
Janssens
Angela M
AM
González-Zuloeta Ladd
Sandra
S
López-Léon
John P A
JP
Ioannidis
Ben A
BA
Oostra
Muin J
MJ
Khoury
Cornelia M
CM
van Duijn
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C505530:CASP8 protein, human; D053181:Caspase 8