Validation in Genetic Association Studies

Validation of genetic associations is understood to be a cornerstone for the scientific credibility of the results. To approach this topic, the general concept of genetic association studies is introduced briefly, followed by how the term 'validation' is used in the context of genetic association studies. As a central issue, reasons for the importance of validation and for failure of validation will be described.

[1]  K. Schulz,et al.  Case-control studies: research in reverse , 2002, The Lancet.

[2]  John P. A. Ioannidis,et al.  Validating, augmenting and refining genome-wide association signals , 2009, Nature Reviews Genetics.

[3]  Michael Boehnke,et al.  Quantifying and correcting for the winner's curse in genetic association studies , 2009, Genetic epidemiology.

[4]  F. Collins,et al.  Genetics moves into the medical mainstream. , 2001, JAMA.

[5]  P. Donnelly,et al.  Replicating genotype–phenotype associations , 2007, Nature.

[6]  Lon R Cardon,et al.  Evaluating coverage of genome-wide association studies , 2006, Nature Genetics.

[7]  Hong-Wen Deng,et al.  Is Replication the Gold Standard for Validating Genome-Wide Association Findings? , 2008, PloS one.

[8]  A Ziegler,et al.  EDITOR Comments on ‘Practical experiences on the necessity of external validation’ , 2008 .

[9]  T. Gingeras,et al.  Flexible use of high-density oligonucleotide arrays for single-nucleotide polymorphism discovery and validation. , 2001, Genome research.

[10]  Jonathan C. Cohen,et al.  A Common Allele on Chromosome 9 Associated with Coronary Heart Disease , 2007, Science.

[11]  Robert C. Elston,et al.  Are Linkage Analysis and the Collection of Family Data Dead? Prospects for Family Studies in the Age of Genome-Wide Association , 2007, Human Heredity.

[12]  Andreas Ziegler,et al.  What Do We Mean by ‘Replication’ and ‘Validation’ in Genome-Wide Association Studies? , 2008, Human Heredity.

[13]  J. Kumar,et al.  Association of polymorphisms in 9p21 region with CAD in North Indian population: replication of SNPs identified through GWAS , 2011, Clinical genetics.

[14]  K. Schulz,et al.  Cohort studies: marching towards outcomes , 2002, The Lancet.

[15]  A. Morris,et al.  Fine mapping versus replication in whole-genome association studies. , 2007, American journal of human genetics.

[16]  Andreas Ziegler,et al.  Genome‐wide association studies: quality control and population‐based measures , 2009, Genetic epidemiology.

[17]  John R Thompson,et al.  Biostatistical Aspects of Genome‐Wide Association Studies , 2008, Biometrical journal. Biometrische Zeitschrift.

[18]  N. Risch.  Searching for genetic determinants in the new millennium , 2000, Nature.

[19]  J. Ioannidis,et al.  STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement , 2009, PLoS medicine.

[20]  Ammarin Thakkinstian,et al.  How to use an article about genetic association: B: Are the results of the study valid? , 2009, JAMA.

[21]  Siobhan M. Dolan,et al.  Assessment of cumulative evidence on genetic associations: interim guidelines. , 2008, International journal of epidemiology.

[22]  J. Ioannidis,et al.  Replication validity of genetic association studies , 2001, Nature Genetics.

[23]  John P.A. Ioannidis,et al.  Non-Replication and Inconsistency in the Genome-Wide Association Setting , 2007, Human Heredity.

[24]  Peter Kraft,et al.  Replication in genome-wide association studies. , 2009, Statistical science : a review journal of the Institute of Mathematical Statistics.

[25]  Peter Kraft,et al.  Curses--winner's and otherwise--in genetic epidemiology. , 2008, Epidemiology.

[26]  Casey S. Greene,et al.  Failure to Replicate a Genetic Association May Provide Important Clues About Genetic Architecture , 2009, PloS one.

[27]  D. Clayton,et al.  Genetic association studies , 2005, The Lancet.

[28]  Andreas Ziegler,et al.  On the Use of the Terms Repeatability and Reproducibility Regarding "Reproducibility of genotypes as measured by the Affymetrix GeneChip(R) 100 K Human Mapping Array Set" by Fridley and colleagues (2008) Comput. Stat. Data Anal. 52: 5367-5374 , 2010, Comput. Stat. Data Anal..

[29]  C. Gieger,et al.  Genomewide association analysis of coronary artery disease. , 2007, The New England journal of medicine.

[30]  A. B. Hill.  The Environment and Disease: Association or Causation? , 1965, Proceedings of the Royal Society of Medicine.

[31]  J. Hirschhorn,et al.  A comprehensive review of genetic association studies , 2002, Genetics in Medicine.

[32]  D. Altman,et al.  Statistic Notes: Regression towards the mean , 1994, BMJ.

[33]  M. Pepe.  The Statistical Evaluation of Medical Tests for Classification and Prediction , 2003 .

[34]  J. Brooks.  Why most published research findings are false: Ioannidis JP, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece , 2008 .

[35]  A. Gylfason,et al.  A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction , 2007, Science.

[36]  Jack Bowden,et al.  Unbiased estimation of odds ratios: combining genomewide association scans with replication studies , 2009, Genetic epidemiology.

[37]  I. König,et al.  A Statistical Approach to Genetic Epidemiology: Concepts and Applications , 2006 .

[38]  Juan P. Casas,et al.  Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies , 2009, PloS one.