Association study designs for complex diseases (original) (raw)
Mullikin, J. C. et al. An SNP map of human chromosome 22. Nature407, 516–520 (2000). CASPubMed Google Scholar
Altshuler, D. et al. An SNP map of the human genome generated by reduced representation shotgun sequencing. Nature407, 513– 516 (2000). CASPubMed Google Scholar
Drews, J. & Ryser, S. The role of innovation in drug development . Nature Biotechnol.15, 1318– 1319 (1997). CAS Google Scholar
Terwilliger, J. D. & Weiss, K. M. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr. Opin. Biotechnol.9, 578–594 ( 1998). CASPubMed Google Scholar
Gambaro, G., Anglani, F. & D'Angelo, A. Association studies of genetic polymorphisms and complex disease. Lancet355, 308– 111 (2000). CASPubMed Google Scholar
Weiss, K. M. & Terwilliger, J. D. How many diseases does it take to map a gene with SNPs? Nature Genet.26, 151–157 (2000).This paper is essential reading for anyone undertaking association studies of common characters. The primary aim is to elucidate the difficulties in identifying genetic loci that contribute to complex traits. The literature cited covers some necessary population genetics material. CASPubMed Google Scholar
Risch, N. J. Searching for genetic determinants in the new millennium. Nature405, 847–856 ( 2000).An excellent summary of current statistical procedures and their comparative strengths and weaknesses for complex trait mapping. Very useful for comparing linkage and association and for distinguishing familial influences on discrete versus quantitative traits. CASPubMed Google Scholar
Schork, N. J., Cardon, L. R. & Xu, X. The future of genetic epidemiology. Trends Genet.14, 266–272 ( 1998). CASPubMed Google Scholar
Collins, F. Positional cloning moves from perditional to traditional. Nature Genet.9, 347–350 ( 1995). CASPubMed Google Scholar
Lander, E. S. & Schork, N. J. Genetic dissection of complex traits. Science265, 2037– 2048 (1994). CASPubMed Google Scholar
Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science273, 1516–1517 (1996). CASPubMed Google Scholar
Jorde, L. B. Linkage disequilibrium and the search for complex disease genes. Genome Res.10, 1435–1444 (2000). CASPubMed Google Scholar
Xiong, M. & Guo, S. W. Fine-scale genetic mapping based on linkage disequilibrium: theory and applications. Am. J. Hum. Genet.60, 1513–1531 ( 1997). CASPubMedPubMed Central Google Scholar
Freimer, N. B. et al. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23. Nature Genet.12, 436–441 (1996). CASPubMed Google Scholar
Hastbacka, J. et al. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nature Genet.2, 204–211 (1992).This is becoming a classic paper on using disequilibrium/haplotype data to identify disease loci. The trait studied does not reflect the common disease framework of current widespread interest, but the procedures used offer a useful model from which to start. CASPubMed Google Scholar
Collins, A., Lonjou, C. & Morton, N. E. Genetic epidemiology of single-nucleotide polymorphisms . Proc. Natl Acad. Sci. USA96, 15173– 15177 (1999).One of a series of key papers by these authors who compare disequilibrium measures, evaluate real data patterns to infer genome-wide marker spacing requirements, and combine population genetics principles with those of disease-gene mapping to characterize allelic association. ArticleCASPubMedPubMed Central Google Scholar
Eaves, I. A. et al. The genetically isolated populations of finland and sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Nature Genet.25, 320– 323 (2000). CASPubMed Google Scholar
Taillon-Miller, P. et al. Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nature Genet.25, 324–328 (2000). CASPubMed Google Scholar
Nickerson, D. A. et al. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nature Genet.19, 233– 240 (1998). CASPubMed Google Scholar
Clark, A. G. et al. Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase. Am. J. Hum. Genet.63, 595–612 (1998). CASPubMedPubMed Central Google Scholar
Cargill, M. et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature Genet.22, 231–238 (1999). CASPubMed Google Scholar
Halushka, M. K. et al. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nature Genet.22, 239–247 (1999). CASPubMed Google Scholar
Templeton, A. R. et al. Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am. J. Hum. Genet.66, 69– 83 (2000). CASPubMedPubMed Central Google Scholar
Chapman, N. H. & Thompson, E. A. Linkage disequilibrium mapping: the role of population history, size, and structure. Adv. Genet.42, 413–437 (2001). CASPubMed Google Scholar
Fisher, R. A. The rhesus factor: a study in scientific method. Am. Sci.35, 95–103 (1947). CASPubMed Google Scholar
Tiwari, J. L. & Terasaki, P. I. HLA and Disease Associations (Springer, New York, 1985). Google Scholar
Risch, N. & Teng, J. Design and analysis of linkage disequilibrium studies for complex human diseases. Am. J. Hum. Genet.61, 1707 (1997). Google Scholar
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.8, 1273–1288 (1998). CASPubMed Google Scholar
Teng, J. & Risch, N. The relative power of family-based and case–control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping. Genome Res.9, 234–241 (1999). CASPubMed Google Scholar
Keavney, B. Genetic association studies in complex diseases. J. Hum. Hypertens.14, 361–367 ( 2000). CASPubMed Google Scholar
Keavney, B. et al. Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators. Lancet355, 434–442 (2000).The need for association studies to involve thousands of patients is clearly shown by comparing the results of a number of typical, small studies with that of a large-scale, well-controlled design. Reference 33 offers a similar example for non-insulin-dependent diabetes mellitus. CASPubMed Google Scholar
Altshuler, D. et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genet.26 , 76–80 (2000). CASPubMed Google Scholar
Cambien, F. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature359, 641–644 ( 1992). CASPubMed Google Scholar
Arnheim, N., Strange, C. & Erlich, H. Use of pooled DNA samples to detect linkage disequilibrium of polymorphic restriction fragments and human disease: studies of the HLA class II loci. Proc. Natl Acad. Sci. USA82, 6970–6974 (1985). CASPubMedPubMed Central Google Scholar
Barcellos, L. F. et al. Association mapping of disease loci, by use of a pooled DNA genomic screen. Am. J. Hum. Genet.61, 734 –747 (1997). CASPubMedPubMed Central Google Scholar
Daniels, J. et al. A simple method for analyzing microsatellite allele image patterns generated from DNA pools and its application to allelic association studies. Am. J. Hum. Genet.62, 1189– 1197 (1998). CASPubMedPubMed Central Google Scholar
Shaw, S. H., Carrasquillo, M. M., Kashuk, C., Puffenberger, E. G. & Chakravarti, A. Allele frequency distributions in pooled DNA samples: applications to mapping complex disease genes. Genome Res.8, 111– 123 (1998). CASPubMed Google Scholar
Kirov, G., Williams, N., Sham, P., Craddock, N. & Owen, M. J. Pooled genotyping of microsatellite markers in parent-offspring trios. Genome Res.10, 105– 115 (2000). CASPubMedPubMed Central Google Scholar
Falk, C. T. & Rubinstein, P. Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations . Ann. Hum. Genet.51, 227– 233 (1987). CASPubMed Google Scholar
Spielman, R. S., McGinnis, R. E. & Ewens, W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus. Am. J. Hum. Genet.52, 506–516 (1993).The TDT test and its immediate predecessors changed the way human genetic studies were conducted throughout the past decade. This is the original paper describing the method. CASPubMedPubMed Central Google Scholar
Spielman, R. S., McGinnis, R. E. & Ewens, W. J. The transmission/disequilibrium test detects cosegregation and linkage. Am. J. Hum. Genet.54, 559– 560 (1994). CASPubMedPubMed Central Google Scholar
Spielman, R. S. & Ewens, W. J. The TDT and other family-based tests for linkage disequilibrium and association. Am. J. Hum. Genet.59, 983–989 (1996). CASPubMedPubMed Central Google Scholar
Sham, P. C. & Curtis, D. An extended transmission/disequilibrium test (TDT) for multiallelic marker loci. Ann. Hum. Genet.59, 323–326 (1995). CASPubMed Google Scholar
Spielman, R. S. & Ewens, W. J. A sibship test for linkage in the presence of association: The sib transmission/disequilibrium test. Am. J. Hum. Genet.62, 450– 458 (1998). CASPubMedPubMed Central Google Scholar
Curtis, D. Use of siblings as controls in case–control association studies. Ann. Hum. Genet.61, 319–333 (1997). CASPubMed Google Scholar
Martin, E. R., Kaplan, N. L. & Weir, B. S. Tests for linkage and association in nuclear families . Am. J. Hum. Genet.61, 439– 448 (1997). CASPubMedPubMed Central Google Scholar
Rabinowitz, D. A transmission disequilibrium test for quantitative trait loci. Hum. Hered.47, 342–350 (1997). CASPubMed Google Scholar
Abecasis, G. R., Cardon, L. R. & Cookson, W. O. A general test of association for quantitative traits in nuclear families. Am. J. Hum. Genet.66, 279–292 (2000). CASPubMed Google Scholar
Martin, E. R., Monks, S. A., Warren, L. L. & Kaplan, N. L. A test for linkage and association in general pedigrees: The pedigree disequilibrium test. Am. J. Hum. Genet.67, 146– 154 (2000). CASPubMedPubMed Central Google Scholar
Pritchard, L. E. et al. Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping. Hum. Mol. Genet.4, 197–202 (1995). CASPubMed Google Scholar
Bennett, S. T. & Todd, J. A. Human type 1 diabetes and the insulin gene: Principles of mapping polygenes. Annu. Rev. Genet.30, 343–370 ( 1996). CASPubMed Google Scholar
Bennett, S. T. et al. Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group. Nature Genet.17, 350–352 (1997). CASPubMed Google Scholar
Merriman, T. R. et al. Transmission of haplotypes of microsatellite markers rather than single marker alleles in the mapping of a putative type 1 diabetes susceptibility gene (IDDM6). Hum. Mol. Genet.7, 517– 524 (1998). CASPubMed Google Scholar
Eaves, I. A. et al. Transmission ratio distortion at the INS-IGF2 VNTR. Nature Genet.22, 324–325 (1999). CASPubMed Google Scholar
Lernmark, A. & Ott, J. Sometimes it's hot, sometimes it's not . Nature Genet.19, 213– 214 (1998). CASPubMed Google Scholar
Goring, H. H. & Terwilliger, J. D. Linkage analysis in the presence of errors IV: joint pseudomarker analysis of linkage and/or linkage disequilibrium on a mixture of pedigrees and singletons when the mode of inheritance cannot be accurately specified. Am. J. Hum. Genet.66, 1310–1327 (2000). CASPubMedPubMed Central Google Scholar
Morton, N.E. & Collins, A. Tests and estimates of allelic association in complex inheritance. Proc. Natl Acad. Sci. USA95 , 11389–93 (1998). CASPubMedPubMed Central Google Scholar
Riordan, J. R. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science245, 1066– 1073 (1989). CASPubMed Google Scholar
Rommens, J. M. et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science245, 1059– 1065 (1989). CASPubMed Google Scholar
Kerem, B. et al. Identification of the cystic fibrosis gene: genetic analysis . Science245, 1073–1080 (1989). CASPubMed Google Scholar
Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell72, 971–983 (1993).
Martin, E. R. et al. SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. Am. J. Hum. Genet.67, 383–394 ( 2000). CASPubMedPubMed Central Google Scholar
Martin, E. R. et al. Analysis of association at single nucleotide polymorphisms in the APOE region. Genomics63, 7– 12 (2000). CASPubMed Google Scholar
Horikawa, Y. et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nature Genet.26, 163–175 (2000). CASPubMed Google Scholar
Roses, A. D. Pharmacogenetics and the practice of medicine. Nature405, 857–865 (2000). CASPubMed Google Scholar
Keavney, B. et al. Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum. Mol. Genet.7, 1745– 1751 (1998).TheACElocus and ACE phenotype is a model quantitative system. Despite the unusually clear haplotype relationships in this gene and population, the study clearly demonstrates the difficulty in distinguishing which specific variants are responsible for phenotypic variability. CASPubMed Google Scholar
Moffatt, M. F., Traherne, J. A., Abecasis, G. R. & Cookson, W. O. Single nucleotide polymorphism and linkage disequilibrium within the TCR alpha/delta locus. Hum. Mol. Genet.9, 1011– 1019 (2000). CASPubMed Google Scholar
Abecasis, G. R. et al. Patterns of linkage disequilibrium from three genomic regions . Am. J. Hum. Genet.68, 191– 197 (2001). CASPubMed Google Scholar
Farrall, M. et al. Fine-mapping of an ancestral recombination breakpoint in DCP1 . Nature Genet.23, 270– 271 (1999). CASPubMed Google Scholar
Abecasis, G. R., Cookson, W. O. & Cardon, L. R. Pedigree tests of transmission disequilibrium. Eur. J. Hum. Genet.8, 545–551 (2000). CASPubMed Google Scholar
Todd, J. A. et al. Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping. Nature338, 587–589 (1989). CASPubMed Google Scholar
Mijovic, C. H., Barnett, A. H. & Todd, J. A. Genetics of diabetes. Trans-racial gene mapping studies . Baillieres Clin. Endocrinol. Metab.5, 321–340 (1991). CASPubMed Google Scholar
Cardon, L. R. & Watkins, H. Waiting for the working draft from the human genome project: A huge achievement, but not of immediate medical use. Br. Med. J.320, 1221– 1222 (2000). Google Scholar
Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet.22, 139– 144 (1999).Mathematical population genetics modelling is used to simulate background levels of linkage disequilibrium in the genome, indicating that very fine-scale maps are required for disease gene association mapping. Although hotly contested and not always supported by empirical reports, this paper clearly outlines the issues and importance of disequilibrium levels in the genome. CASPubMed Google Scholar
Collins, A. & Morton, N. E. Mapping a disease locus by allelic association. Proc. Natl Acad. Sci. USA95, 1741–1745 (1998). CASPubMedPubMed Central Google Scholar
Cox, N. J. et al. Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. Nature Genet.21, 213–215 ( 1999). CASPubMed Google Scholar
Risch, N. Evolving methods in genetic epidemiology. 2. Genetic linkage from an epidemiologic perspective. Epidemiol. Rev.19, 24– 32 (1997). CASPubMed Google Scholar
Potter, J. D. At the interfaces of epidemiology, genetics and genomics. Nature Rev. Genet.2, 142–147 ( 2001). CASPubMed Google Scholar
Khoury, M. J., Beaty, T. H. & Cohen, B. H. Fundamentals of Genetic Epidemiology (Oxford Univ. Press, Oxford, 1993). Google Scholar
Huttley, G. A., Smith, M. W., Carrington, M. & O'Brien, S. J. A scan for linkage disequilibrium across the human genome. Genetics152, 1711–1722 ( 1999). CASPubMedPubMed Central Google Scholar
Goddard, K. A., Hopkins, P. J., Hall, J. M. & Witte, J. S. Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations. Am. J. Hum. Genet.66, 216–234 (2000). CASPubMedPubMed Central Google Scholar
Majewski, J. & Ott, J. GT repeats are associated with recombination on human chromosome 22. Genome Res.10, 1108–1114 (2000). CASPubMedPubMed Central Google Scholar
Hartl, D. L. & Clark, A. G. Principles of Population Genetics (Sinauer Associates, Sunderland, MA, 1997). Google Scholar
Pritchard, J. K. & Rosenberg, N. A. Use of unlinked genetic markers to detect population stratification in association studies . Am. J. Hum. Genet.65, 220– 228 (1999).This paper describes the use of unlinked genetic markers to detect population stratification, with minimal mathematical complexity. The key issues of marker spacing and informativeness are evaluated in detail. Reference94should be read in follow-up of this paper to see how stratification can be accounted for when it is present. CASPubMedPubMed Central Google Scholar
Devlin, B. & Roeder, K. Genomic control for association studies . Biometrics55, 997–1004 (1999). CASPubMed Google Scholar
Pritchard, J. K., Stephens, M. & Donnelly, P. Inference of population structure using multilocus genotype data. Genetics155, 945– 959 (2000). CASPubMedPubMed Central Google Scholar
Pritchard, J. K., Stephens, M., Rosenberg, N. A. & Donnelly, P. Association mapping in structured populations. Am. J. Hum. Genet.67, 170–181 ( 2000). CASPubMedPubMed Central Google Scholar