Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2008 Feb;32(2):179-85.
doi: 10.1002/gepi.20292.

Genome-wide significance for dense SNP and resequencing data

Clive J Hoggart  1 , Taane G Clark, Maria De Iorio, John C Whittaker, David J Balding
Affiliations
Comparative Study

Genome-wide significance for dense SNP and resequencing data

Clive J Hoggart et al. Genet Epidemiol. 2008 Feb.

Abstract

The problem of multiple testing is an important aspect of genome-wide association studies, and will become more important as marker densities increase. The problem has been tackled with permutation and false discovery rate procedures and with Bayes factors, but each approach faces difficulties that we briefly review. In the current context of multiple studies on different genotyping platforms, we argue for the use of truly genome-wide significance thresholds, based on all polymorphisms whether or not typed in the study. We approximate genome-wide significance thresholds in contemporary West African, East Asian and European populations by simulating sequence data, based on all polymorphisms as well as for a range of single nucleotide polymorphism (SNP) selection criteria. Overall we find that significance thresholds vary by a factor of >20 over the SNP selection criteria and statistical tests that we consider and can be highly dependent on sample size. We compare our results for sequence data to those derived by the HapMap Consortium and find notable differences which may be due to the small sample sizes used in the HapMap estimate.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Addressing population-specific multiple testing burdens in genetic association studies.
    Sobota RS, Shriner D, Kodaman N, Goodloe R, Zheng W, Gao YT, Edwards TL, Amos CI, Williams SM. Sobota RS, et al. Ann Hum Genet. 2015 Mar;79(2):136-47. doi: 10.1111/ahg.12095. Epub 2015 Jan 22. Ann Hum Genet. 2015. PMID: 25644736 Free PMC article.
  • Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
    Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T; Global BPgen Consortium; Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY. Ikram MK, et al. PLoS Genet. 2010 Oct 28;6(10):e1001184. doi: 10.1371/journal.pgen.1001184. PLoS Genet. 2010. PMID: 21060863 Free PMC article.
  • Genome-wide association studies in Alzheimer's disease: a review.
    Tosto G, Reitz C. Tosto G, et al. Curr Neurol Neurosci Rep. 2013 Oct;13(10):381. doi: 10.1007/s11910-013-0381-0. Curr Neurol Neurosci Rep. 2013. PMID: 23954969 Free PMC article. Review.
  • Pleiotropy of cancer susceptibility variants on the risk of non-Hodgkin lymphoma: the PAGE consortium.
    Lim U, Kocarnik JM, Bush WS, Matise TC, Caberto C, Park SL, Carlson CS, Deelman E, Duggan D, Fesinmeyer M, Haiman CA, Henderson BE, Hindorff LA, Kolonel LN, Peters U, Stram DO, Tiirikainen M, Wilkens LR, Wu C, Kooperberg C, Le Marchand L. Lim U, et al. PLoS One. 2014 Mar 5;9(3):e89791. doi: 10.1371/journal.pone.0089791. eCollection 2014. PLoS One. 2014. PMID: 24598796 Free PMC article.
  • Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder.
    Belmonte Mahon P, Pirooznia M, Goes FS, Seifuddin F, Steele J, Lee PH, Huang J, Hamshere ML; Bipolar Genome Study (BiGS) Consortium, The Wellcome Trust Case Control Consortium Bipolar Disorder Group; Depaulo JR Jr, Kelsoe JR, Rietschel M, Nöthen M, Cichon S, Gurling H, Purcell S, Smoller JW, Craddock N, Schulze TG, McMahon FJ, Potash JB, Zandi PP. Belmonte Mahon P, et al. Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):370-8. doi: 10.1002/ajmg.b.31172. Epub 2011 Feb 8. Am J Med Genet B Neuropsychiatr Genet. 2011. PMID: 21305692 Free PMC article.
See all "Cited by" articles

Publication types

LinkOut - more resources