Pathway-based approaches for analysis of genomewide association studies.

Published genomewide association (GWA) studies typically analyze and report single-nucleotide polymorphisms (SNPs) and their neighboring genes with the strongest evidence of association (the "most-significant SNPs/genes" approach), while paying little attention to the rest. Borrowing ideas from microarray data analysis, we demonstrate that pathway-based approaches, which jointly consider multiple contributing factors in the same pathway, might complement the most-significant SNPs/genes approach and provide additional insights into interpretation of GWA data on complex diseases.

[1]  Douglas A. Wolfe,et al.  Nonparametric Statistical Methods , 1973 .

[2]  R. Simes,et al.  An improved Bonferroni procedure for multiple tests of significance , 1986 .

[3]  N Risch,et al.  The Future of Genetic Studies of Complex Human Diseases , 1996, Science.

[4]  S. Sarkar,et al.  The Simes Method for Multiple Hypothesis Testing with Positively Dependent Test Statistics , 1997 .

[5]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[6]  M. Ashburner,et al.  The Gene Ontology Consortium , 2000 .

[7]  M. Gottesman,et al.  Overview: ABC Transporters and Human Disease , 2001, Journal of bioenergetics and biomembranes.

[8]  E. Zenteno,et al.  O‐Glycosylation in Sprouting Neurons in Alzheimer Disease, Indicating Reactive Plasticity , 2001, Journal of neuropathology and experimental neurology.

[9]  Yoav Benjamini,et al.  Identifying differentially expressed genes using false discovery rate controlling procedures , 2003, Bioinform..

[10]  Jurg Ott,et al.  Sum statistics for the joint detection of multiple disease loci in case‐control association studies with SNP markers , 2003, Genetic epidemiology.

[11]  M. Hofker.  Faculty Opinions recommendation of PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. , 2003 .

[12]  P Jeffrey Conn,et al.  Glutamate Receptors and Parkinson’s Disease , 2003, Drugs & aging.

[13]  R. Bendayan,et al.  Functional Expression and Localization of P-glycoprotein in the Central Nervous System: Relevance to the Pathogenesis and Treatment of Neurological Disorders , 2004, Pharmaceutical Research.

[14]  Nathaniel Rothman,et al.  Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. , 2004, Journal of the National Cancer Institute.

[15]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[16]  Mariza de Andrade,et al.  High-resolution whole-genome association study of Parkinson disease. , 2005, American journal of human genetics.

[17]  T. Lefebvre,et al.  Does O-GlcNAc play a role in neurodegenerative diseases? , 2005, Expert review of proteomics.

[18]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Dmitri V Zaykin,et al.  Ranks of Genuine Associations in Whole-Genome Scans , 2005, Genetics.

[20]  M. Orešič,et al.  Pathways to the analysis of microarray data. , 2005, Trends in biotechnology.

[21]  G. Abecasis,et al.  A note on exact tests of Hardy-Weinberg equilibrium. , 2005, American journal of human genetics.

[22]  Sonja W. Scholz,et al.  Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data , 2006, The Lancet Neurology.

[23]  M. Daly,et al.  Evaluating and improving power in whole-genome association studies using fixed marker sets , 2006, Nature Genetics.

[24]  Philip S Rosenberg,et al.  Resampling‐based multiple hypothesis testing procedures for genetic case‐control association studies , 2006, Genetic epidemiology.

[25]  Larry Wasserman,et al.  Using linkage genome scans to improve power of association in genome scans. , 2006, American journal of human genetics.

[26]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[27]  Richard H. P. Porter,et al.  Glutamate and Parkinson’s disease , 1996, Molecular Neurobiology.

[28]  Á. Carracedo,et al.  Complement factor H. , 2007, Ophthalmology.

[29]  Gerald W. Hart,et al.  Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins , 2007, Nature.

[30]  G. Hart,et al.  Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. , 2007, Nature.

[31]  Chiara Sabatti,et al.  Human genetics: Variants in common diseases , 2007, Nature.