From Single-SNP to Wide-Locus: Genome-Wide Association Studies Identifying Functionally Related Genes and Intragenic Regions in Small Sample Studies

• Collins FS , GreenED, GuttmacherAE, GuyerMS. A vision for the future of genomics research. Nature422(6934) , 835–847 (2003).
   PubMed Web of Science ®Google Scholar
• Klein RJ , ZeissC, ChewEY et al. Complement factor H polymorphism in age-related macular degeneration. Science 308(5720) , 385–389 (2005).
   PubMed Web of Science ®Google Scholar
• Sullivan P . Don‘t give up on GWAS. Mol. Psychiatry17(1) , 2–3 (2012).
   PubMed Web of Science ®Google Scholar
• Klein C , LohmannK, ZieglerA. The promise and limitations of genome-wide association studies. JAMA308(18) , 1867–1868 (2012).
   Web of Science ®Google Scholar
• Cichon S , CraddockN, DalyM et al.; Psychiatric GWAS Consortium Coordinating Committee. Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am. J. Psychiatry166(5) , 540–556 (2009).
   PubMed Web of Science ®Google Scholar
• Meehl PE . Theoretical risks and tabular asterisks: Sir Karl, Sir Ronald, and the slow progress of soft psychology. J. Consult. Clin. Psychol.46 , 806–834 (1978).
   Web of Science ®Google Scholar
• Waller NG . The fallacy of the null hypothesis in soft psychology. Appl. Prev. Psychol.11 , 83–86 (2004).
   Google Scholar
• Hoh J , OttJ. Mathematical multi-locus approaches to localizing complex human trait genes. Nat. Rev. Genet.4(9) , 701–709 (2003).
   PubMed Web of Science ®Google Scholar
• Fisher RA . The correlation between relatives on the supposition of Mendelian inheritance. Transactions of the Royal Society of Edinburgh52 , 399–433 (1918).
   Google Scholar
• Goldstein DB . Common Genetic Variation and Human Traits. N. Engl. J. Med.360(17) , 1696–1698 (2009).
   PubMed Web of Science ®Google Scholar
• Ballard DH , ChoJ, ZhaoHY. Comparisons of multi-marker association methods to detect association between a candidate region and disease. Genet. Epidemiol.34(3) , 201–212 (2009).
   Web of Science ®Google Scholar
• Bechhofer RE . A single-sample multiple decision procedure for ranking means of normal populations with known variances. Ann. Math. Statist.25 , 16–39 (1954).
   Google Scholar
• Rosenthal R . Cumulating evidence. In: A Handbook For Data Analysis in the Behavioral Sciences: Methodological Issues. Keren G, Lewis C (Eds). Erlbaum, NJ, USA, 519–559 (1993).
   Google Scholar
• Morales JF , SongT, AuerbachAD, WittkowskiKM. Phenotyping genetic diseases using an extension of µ-scores for multivariate data. Stat. Appl. Genet. Mol.7(1) , 19 (2008).
   PubMedGoogle Scholar
• Lawrence R , EvansDM, MorrisAP et al. Genetically indistinguishable SNPs and their influence on inferring the location of disease-associated variants. Genome Res. 15(11) , 1503–1510 (2005).
   PubMed Web of Science ®Google Scholar
• A second generation human haplotype map of over 3.1 million SNPs. Nature449(7164) , 851–861 (2007).
   PubMed Web of Science ®Google Scholar
• Mann HB , WhitneyDR. On a test of whether one of two random variables is stochastically larger than the other. Ann. Math. Statist.18(1) , 50–60 (1947).
   Google Scholar
• Hoeffding W . A class of statistics with asymptotically normal distribution. Ann. Math. Statist.19 , 293–325 (1948).
   Google Scholar
• Li H . U-statistics in genetic association studies. Hum. Genet.131(9) , 1395–1401 (2012).
   PubMed Web of Science ®Google Scholar
• Pearson TA , ManolioTA. How to interpret a genome-wide association study. JAMA299(11) , 1335–1344 (2008).
   PubMed Web of Science ®Google Scholar
• Wittkowski KM , SongT, AndersonK, DanielsJE. U-scores for multivariate data in sports. J. Quant. Anal. Sports4(3) , 7 (2008).
   Google Scholar
• Diana M , SongT, WittkowskiKM. Studying travel-related individual assessments and desires by combining hierarchically structured ordinal variables. Transportation36(2) , 187–206 (2009).
   PubMed Web of Science ®Google Scholar
• Hilton JF . The appropriateness of the Wilcoxon test in ordinal data. Stat. Med.15(6) , 631–645 (1996).
   PubMed Web of Science ®Google Scholar
• Loiseau P , PanayiotopoulosCP, HirschE. Childhood absence epilepsy and related syndromes. In: Epilepsy Syndromes in Infancy, Childhood and Adolescence. Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P (Eds). John Libbey, Montrouge, France, 285–303 (2002).
   Google Scholar
• Glauser TA , CnaanA, ShinnarS et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N. Engl. J. Med. 362(9) , 790–799 (2010).
   PubMed Web of Science ®Google Scholar
• Kim JE , ChoiHC, SongHK et al. Levetiracetam inhibits interleukin-1 beta inflammatory responses in the hippocampus and piriform cortex of epileptic rats. Neurosci. Lett. 471(2) , 94–99 (2010).
   PubMed Web of Science ®Google Scholar
• Akaike H . A new look at statistical-model identification. IEEE Trans. Autom. ControlAC19(6) , 716–723 (1974).
   Web of Science ®Google Scholar
• Lehmann EL . Some model I problems of selection. Annals of Mathematical Statistics32 , 990–1012 (1961).
   Google Scholar
• Friedman JI , VrijenhoekT, MarkxS et al. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol. Psychiatry13(3) , 261–266 (2008).
   PubMed Web of Science ®Google Scholar
• Crunelli V , LerescheN. Childhood absence epilepsy: genes, channels, neurons and networks. Nat. Rev. Neurosci.3(5) , 371–382 (2002).
   PubMed Web of Science ®Google Scholar
• van Bokhoven H . Genetic and epigenetic networks in intellectual disabilities. Annu. Rev. Genet.45 , 81–104 (2011).
   PubMed Web of Science ®Google Scholar
• Oprica M , ErikssonC, SchultzbergM. Inflammatory mechanisms associated with brain damage induced by kainic acid with special reference to the interleukin-1 system. J. Cell Mol. Med.7(2) , 127–140 (2003).
   PubMed Web of Science ®Google Scholar
• Yuan J , Wang L-Y, Li J-M et al. Altered expression of the small guanosine triphosphatase RhoA in human temporal lobe epilepsy. J. Mol. Neurosci.42(1) , 53–58 (2010).
   PubMed Web of Science ®Google Scholar
• Lim J , HaoT, ShawC et al. A protein–protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125(4) , 801–814 (2006).
   PubMed Web of Science ®Google Scholar
• Billuart P , BienvenuT, RonceN et al. Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392(6679) , 923–926 (1998).
   PubMed Web of Science ®Google Scholar
• Gribaa M , SalihM, AnheimM et al. A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21–q23. Brain 130(7) , 1921–1928 (2007).
   PubMedGoogle Scholar
• Imbrici P , JaffeSL, EunsonLH et al. Dysfunction of the brain calcium channel Ca(V)2.1 in absence epilepsy and episodic ataxia. Brain 127 , 2682–2692 (2004).
   PubMed Web of Science ®Google Scholar
• Tentler D , GustavssonP, LeistiJ et al. Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia. Eur. J. Hum. Genet. 7(5) , 541–548 (1999).
   PubMed Web of Science ®Google Scholar
• Bergmann C , ZerresK, SenderekJ et al. Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. Brain 126(Pt 7) , 1537–1544 (2003).
   PubMed Web of Science ®Google Scholar
• Hayashi T , OkabeT, Nasu-NishimuraY et al. PX-RICS, a novel splicing variant of RICS, is a main isoform expressed during neural development. Genes Cells 12(8) , 929–939 (2007).
   PubMed Web of Science ®Google Scholar
• Nakamura T , HayashiT, Mimori-KiyosueY et al. The PX-RICS-14–13–3 zeta/theta complex couples N-cadherin-beta-catenin with dynein-dynactin to mediate its export from the endoplasmic reticulum. J. Biol. Chem. 285(21) , 16145–16154 (2010).
   PubMed Web of Science ®Google Scholar
• Wang K , ZhangH, KugathasanS et al. Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn disease. Am. J. Hum. Genet. 84(3) , 399–405 (2009).
   PubMed Web of Science ®Google Scholar
• Subramanian A , TamayoP, MoothaV et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102(43) , 15545–15550 (2005).
   PubMed Web of Science ®Google Scholar
• Ketzef M , KahnJ, WeissbergI, BeckerAJ, FriedmanA, GitlerD. Compensatory network alterations upon onset of epilepsy in synapsin triple knock-out mice. Neuroscience189 , 108–122 (2011).
   PubMed Web of Science ®Google Scholar
• Courtney KD , CorcoranRB, EngelmanJA. The PI3K pathway as drug target in human cancer. J. Clin. Oncol.28(6) , 1075–1083 (2010).
   PubMed Web of Science ®Google Scholar
• Harris SJ , FosterJG, WardSG. PI3K isoforms as drug targets in inflammatory diseases: lessons from pharmacological and genetic strategies. Curr. Opin. Investig. Drugs10(11) , 1151–1162 (2009).
   PubMed Web of Science ®Google Scholar
• Xue Y , XieN, CaoL, ZhaoX, JiangH, ChiZ. Diazoxide preconditioning against seizure-induced oxidative injury is via the PI3K/Akt pathway in epileptic rat. Neurosci. Lett.495(2) , 130–134 (2011).
   PubMed Web of Science ®Google Scholar
• Nasu-Nishimura Y , HayashiT, OhishiT et al. Role of the Rho GTPase-activating protein RICS in neurite outgrowth. Genes Cells 11(6) , 607–614 (2006).
   PubMed Web of Science ®Google Scholar
• Schubbert S , ShannonK, BollagG. Hyperactive Ras in developmental disorders and cancer. Nat. Rev. Cancer7(4) , 295–308 (2007).
   PubMed Web of Science ®Google Scholar

▪ Websites

• A Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment-Resistant Partial Epilepsy. http://clinicaltrials.gov/ct2/show/NCT01501383
   Google Scholar
• Illumina. Science / Illumina iControlDB. www.illumina.com/science/icontroldb.ilmn
   Google Scholar
• A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer. http://clinicaltrials.gov/show/NCT01331083
   Google Scholar