• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of ajhgLink to Publisher's site
Am J Hum Genet. Jun 2000; 66(6): 1933–1944.
Published online May 8, 2000. doi:  10.1086/302929
PMCID: PMC1378064

The power of genomic control.


Although association analysis is a useful tool for uncovering the genetic underpinnings of complex traits, its utility is diminished by population substructure, which can produce spurious association between phenotype and genotype within population-based samples. Because family-based designs are robust against substructure, they have risen to the fore of association analysis. Yet, if population substructure could be ignored, this robustness can come at the price of power. Unfortunately it is rarely evident when population substructure can be ignored. Devlin and Roeder recently have proposed a method, termed "genomic control" (GC), which has the robustness of family-based designs even though it uses population-based data. GC uses the genome itself to determine appropriate corrections for population-based association tests. Using the GC method, we contrast the power of two study designs, family trios (i.e., father, mother, and affected progeny) versus case-control. For analysis of trios, we use the TDT test. When population substructure is absent, we find GC is always more powerful than TDT; furthermore, contrary to previous results, we show that as a disease becomes more prevalent the discrepancy in power becomes more extreme. When population substructure is present, however, the results are more complex: TDT is more powerful when population substructure is substantial, and GC is more powerful otherwise. We also explore general issues of power and implementation of GC within the case-control setting and find that, economically, GC is at least comparable to and often less expensive than family-based methods. Therefore, GC methods should prove a useful complement to family-based methods for the genetic analysis of complex traits.

Full Text

The Full Text of this article is available as a PDF (261K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Collins FS, Patrinos A, Jordan E, Chakravarti A, Gesteland R, Walters L. New goals for the U.S. Human Genome Project: 1998-2003. Science. 1998 Oct 23;282(5389):682–689. [PubMed]
  • Devlin B, Roeder K. Genomic control for association studies. Biometrics. 1999 Dec;55(4):997–1004. [PubMed]
  • Devlin B, Risch N, Roeder K. Statistical evaluation of DNA fingerprinting: a critique of the NRC's report. Science. 1993 Feb 5;259(5096):748–837. [PubMed]
  • Ewens WJ, Spielman RS. The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet. 1995 Aug;57(2):455–464. [PMC free article] [PubMed]
  • Houwen RH, Baharloo S, Blankenship K, Raeymaekers P, Juyn J, Sandkuijl LA, Freimer NB. Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis. Nat Genet. 1994 Dec;8(4):380–386. [PubMed]
  • Knapp M. A note on power approximations for the transmission/disequilibrium test. Am J Hum Genet. 1999 Apr;64(4):1177–1185. [PMC free article] [PubMed]
  • Morton NE. Genetic structure of forensic populations. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2556–2560. [PMC free article] [PubMed]
  • Morton NE, Collins A. Tests and estimates of allelic association in complex inheritance. Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11389–11393. [PMC free article] [PubMed]
  • Puffenberger EG, Kauffman ER, Bolk S, Matise TC, Washington SS, Angrist M, Weissenbach J, Garver KL, Mascari M, Ladda R, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. 1994 Aug;3(8):1217–1225. [PubMed]
  • Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990 Feb;46(2):222–228. [PMC free article] [PubMed]
  • Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996 Sep 13;273(5281):1516–1517. [PubMed]
  • Risch N, Teng J. The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling. Genome Res. 1998 Dec;8(12):1273–1288. [PubMed]
  • Slager SL, Huang J, Vieland VJ. Effect of allelic heterogeneity on the power of the transmission disequilibrium test. Genet Epidemiol. 2000 Feb;18(2):143–156. [PubMed]
  • Spielman RS, McGinnis RE, Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed]
  • Suarez BK, Rice J, Reich T. The generalized sib pair IBD distribution: its use in the detection of linkage. Ann Hum Genet. 1978 Jul;42(1):87–94. [PubMed]
  • Wang DG, Fan JB, Siao CJ, Berno A, Young P, Sapolsky R, Ghandour G, Perkins N, Winchester E, Spencer J, et al. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science. 1998 May 15;280(5366):1077–1082. [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...