A new approach to the problem of multiple comparisons in the genetic dissection of complex traits
- PMID: 9832544
- PMCID: PMC1460417
- DOI: 10.1093/genetics/150.4.1699
A new approach to the problem of multiple comparisons in the genetic dissection of complex traits
Abstract
Saturated genetic marker maps are being used to map individual genes affecting quantitative traits. Controlling the "experimentwise" type-I error severely lowers power to detect segregating loci. For preliminary genome scans, we propose controlling the "false discovery rate," that is, the expected proportion of true null hypotheses within the class of rejected null hypotheses. Examples are given based on a granddaughter design analysis of dairy cattle and simulated backcross populations. By controlling the false discovery rate, power to detect true effects is not dependent on the number of tests performed. If no detectable genes are segregating, controlling the false discovery rate is equivalent to controlling the experimentwise error rate. If quantitative loci are segregating in the population, statistical power is increased as compared to control of the experimentwise type-I error. The difference between the two criteria increases with the increase in the number of false null hypotheses. The false discovery rate can be controlled at the same level whether the complete genome or only part of it has been analyzed. Additional levels of contrasts, such as multiple traits or pedigrees, can be handled without the necessity of a proportional decrease in the critical test probability.
Comment in
-
Using the false discovery rate approach in the genetic dissection of complex traits: a response to Weller et al.Genetics. 2000 Apr;154(4):1917-8. doi: 10.1093/genetics/154.4.1917. Genetics. 2000. PMID: 10950641 Free PMC article. No abstract available.
Similar articles
-
Multiple quantitative trait loci mapping with cofactors and application of alternative variants of the false discovery rate in an enlarged granddaughter design.Genetics. 2004 Oct;168(2):1019-27. doi: 10.1534/genetics.104.030296. Genetics. 2004. PMID: 15514072 Free PMC article.
-
Determination of quantitative trait nucleotides by concordance analysis between quantitative trait loci and marker genotypes of US Holsteins.J Dairy Sci. 2018 Oct;101(10):9089-9107. doi: 10.3168/jds.2018-14816. Epub 2018 Jul 19. J Dairy Sci. 2018. PMID: 30031583
-
Whole genome scan to detect chromosomal regions affecting multiple traits in dairy cattle.J Dairy Sci. 2004 Oct;87(10):3550-60. doi: 10.3168/jds.S0022-0302(04)73492-X. J Dairy Sci. 2004. PMID: 15377635
-
Novel linkage mapping approach using DNA pooling in human and animal genetics. II. Detection of quantitative traits loci in dairy cattle.J Appl Genet. 2002;43(3):309-18. J Appl Genet. 2002. PMID: 12177520 Review.
-
Role of the bovine immune system and genome in resistance to gastrointestinal nematodes.Vet Parasitol. 2001 Jul 12;98(1-3):51-64. doi: 10.1016/s0304-4017(01)00423-x. Vet Parasitol. 2001. PMID: 11516579 Review.
Cited by
-
Genetic association studies in cancer: good, bad or no longer ugly?Hum Genomics. 2006 Jun;2(6):415-21. doi: 10.1186/1479-7364-2-6-415. Hum Genomics. 2006. PMID: 16848979 Free PMC article. Review.
-
Genetic architecture of nest building in mice LG/J × SM/J.Front Genet. 2012 May 28;3:90. doi: 10.3389/fgene.2012.00090. eCollection 2012. Front Genet. 2012. PMID: 22654894 Free PMC article.
-
Multiplexed protein measurement: technologies and applications of protein and antibody arrays.Nat Rev Drug Discov. 2006 Apr;5(4):310-20. doi: 10.1038/nrd2006. Nat Rev Drug Discov. 2006. PMID: 16582876 Free PMC article. Review.
-
False discovery rate in linkage and association genome screens for complex disorders.Genetics. 2003 Jun;164(2):829-33. doi: 10.1093/genetics/164.2.829. Genetics. 2003. PMID: 12807801 Free PMC article.
-
Neuroanatomical correlates of intelligence in healthy young adults: the role of basal ganglia volume.PLoS One. 2014 Apr 3;9(4):e93623. doi: 10.1371/journal.pone.0093623. eCollection 2014. PLoS One. 2014. PMID: 24699871 Free PMC article.
References
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources