Abstract
The genetic analysis of quantitative traits in humans is changing as a result of the availability of whole-genome SNP data. Heritability analysis can make use of actual genetic sharing between pairs of individuals estimated from the genotype data, rather than the expected genetic sharing implied by their family relationship. This could provide more accurate heritability estimates and help to overcome the equal environment assumption. Quantitative trait locus (QTL) linkage mapping can make use of local genetic sharing inferred from very dense local genotype data from pedigree members or individuals not previously known to be related. This approach may be particularly suited for detecting loci that contain rare variants with major effect on the phenotype. Finally, whole-genome SNP data can be used to measure the genetic similarity between individuals to provide matched sets for association studies, in order to avoid spurious association from population stratification.
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References
Abecasis GR, Cardon LR, Cookson WO (2000a) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66(1):279–292
Abecasis GR, Cookson WO, Cardon LR (2000b) Pedigree tests of transmission disequilibrium. Eur J Hum Genet 8(7):545–551
Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101
Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211
Amos CI (1994) Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet 54:535–543
Carlson C, Eberle M, Rieder M, Yi Q, Kruglyak L, Nickerson D (2004) Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74:106–120
Falconer DS, Mackay TFC (1996) Environmental variance. In: Introduction to quantitative genetics. Longman, London, pp 136–142
Fisher RA (1918) The correlation between relatives on the supposition of Mendelian inheritance. Trans R Soc Edinb 52:399–433
Fulker DW, Cherny SS (1996) An improved multipoint sib-pair analysis of quantitative traits. Behav Genet 26:527–532
Fulker DW, Cherny SS, Sham PC, Hewitt JK (1999) Combined linkage and association sib-pair analysis for quantitative traits. Am J Hum Genet 64(1):259–267
Gabriel S, Schaffner S, Nguyen H, Moore J, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero S, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander E, Daly M, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229
Horvath S, Xu X, Laird N (2001) The family based association test method: strategies for studying general genotype–phenotype associations. Eur J Hum Genet 9:301–306
Kruglyak L, Lander ES (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet 57:439–454
Kruglyak L, Daly MJ, Lander ES (1995) Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet 56:519–527
Li M, Li C, Guan W (2008) Evaluation of coverage variation of SNP chips for genome-wide association studies. Eur J Hum Genet 16(5):635–643
Lynch M, Walsh JB (1998) Genetics and analysis of quantitative traits. Sinauer Associates, Sunderland
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575
Sham P, Ao S, Kwan J, Kao P, Cheung F, Fong P, Ng M (2007) Combining functional and linkage disequilibrium information in the selection of tag SNPs. Bioinformatics 23:129–131
The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320
The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449:851–861
Visscher P, Medland S, Ferreira M, Morley K, Zhu G, Cornes B, Montgomery G, Martin N (2006) Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings. PLoS Genet 2:e41
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We acknowledge support from grant EY-12562 from the National Insitutes of Health, USA, to PCS and SSC.
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Sham, P.C., Cherny, S.S. & Purcell, S. Application of genome-wide SNP data for uncovering pairwise relationships and quantitative trait loci. Genetica 136, 237–243 (2009). https://doi.org/10.1007/s10709-008-9349-4
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DOI: https://doi.org/10.1007/s10709-008-9349-4