집단 및 가족기반연구에서의 유전적 연관성 분석 고찰: 방법론과 소프트웨어
A Review of Genetic Association Analyses in Population and Family Based Data: Methods and Software
최근 단일염기다형성 및 일배체형을 이용한 질병-유전자간 연관성연구가 많이 진행되고 있으며, 이를 위한 다양한 분석방법과 분석도구가 개발되고 있다. 그러나 통합 소프트웨어는 충분히 확립되지 못하였으며, 각 소프트웨어가 제공하는 분석방법 및 양식에 차이가 많아 연구자가 적절한 것을 선택하기가 쉽지 않다. 본고에서는 유전적 연관성연구를 사전분석단계, 집단기반연구방법, 가족기반연구방법으로 나누어 각각의 목적에 따른 분석방법을 고찰하고, 이의 분석을 위한 주요 소프트웨어로서 FBAT, SAS/Genetics, SAGE, R의 지원내용과 방법을 비교하였다.
Recently, there have been lots of study for disease-genetic association using SNPs and haplotypes. Statistical methods and tools for various types of data are developed by many researchers. However, there is no unified software which can handle most of major analysis, and the methods and manners to deal with data are quite different through softwares. And thus it is not easy to researcher to choose proper software. In this study, we devide analyzing procedures into three steps: preliminary analysis, population-based analysis and family-based analysis. We review the statistical methods for each step and compare the features of the FBAT, SAS/Genetics, SAGE and R as major integrating softwares for genetic study.
- Abecasis, G. R., Cardon, L. R. and Cookson, W. O. (2000). A general test of association for quantitative traits in nuclear families, American Journal of Human Genetics, 66, 279-292.
- Abecasis, G. R., Cherny, S. S., Cookson, W. O. and Cardon, L. R. (2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees, Nature Genetics, 30, 97-101.
- Allison, D. B. (1997). Transmission-disequilibrium tests for quantitative traits, American Journal of Human Genetics, 60, 676-690.
- Allison, D. B., Hero, M., Kaplan, N. and Martin, E. R. (1999). Sibling-based test of linkage and association for quantitative trials, American Journal of Human Genetics, 64, 1754-1764.
- Balding, D. J. (2006). A tutorial on statistical methods for population association studies, Nature Reviews Genetics, 7, 781-91.
- Barrett, J. C., Fry, B., Maller, J. and Daly, M. J. (2005). Haploview: Analysis and visualization of LD and haplotype maps, Bioinformatics, 21, 263-265.
- Clark, A. G. (1990). Inference of haplotypes from PCR-amplified samples of diploid populations, Molecular Biology and Evolution, 7, 111-122.
- Clayton, D. (1999). A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission, American Journal of Human Genetics, 65, 1170-1177.
- Curtis, D. (1997). Use of siblings as controls in case-control association studies, Annals of Human Genetics, 61, 319-333.
- Curtis, D. and Sham, P. C. (1995). An extended transmission/disequilibrium Test(TDT) for multi-allele marker loci, Genetic Epidemiology, 7, 319-334.
- Czika, W., Yu, X. and Wolfinger, R. D. (2002). A introduction to genetic data analysis using SAS/Genetics, SAS Institute Inc., Cary, North Carolina, USA.
- Elston, R. C. (2008). Statistical analysis for genetic epidemiology(S.A.G.E.) user reference manual (Version 5.4.2), Case Western Reserve University, Cleveland, Ohio.
- Elston, R. C., George, V. T. and Severtson, F. (1992). The Elston-Stewart algorithm for continuous genotypes and environmental factors, Human Heredity, 42, 16-27.
- Ewens, W. J., Li, M. and Spielman, R. S. (2008). A review of family-based tests for linkage disequilibrium between a quantitative trait and a genetic marker, PLoS Genetics, 4, e1000180.
- Fallin, D. and Schrock, N. J. (2000). Accuaracy of haplotype frequency estimation of biallelic loci, via the expectaation-maxmization algorithm for inphased diploid genotype data, American Journal of Human Genetics, 67, 947-959.
- French, B., Lumley, T., Monks, S. A., Rice, K. M., Hindorff, L. A., Reiner, A. P. and Psaty, B. M. (2006). Simple estimates of haplotype relative risks in case-control data, Genetic Epidemiology, 30, 485-494.
- Fulker, D. W., Cherny, S. S., Sham, P. C. and Hewitt, J. K. (1999). Combined linkage and association sib-pair analysis for quantitative traits, American Journal of Human Genetics, 64, 259-267.
- George, V. T., Tiwari, H. K., Zhu, X. and Elston, R. C. (1999). A test of transmission/disequilibrium for quantitative traits in pedigree data by multiple regression, American Journal of Human Genetics, 65, 236-245.
- Gonzalez, J. R., Armengol, L., Sole, X., Guino, E., Mercader, J. M., Estivill, X. and Moreno, V. (2007). SNPassoc: an R package to perform whole genome association studies, Bioinformatics, 23, 654-655.
- Guo, S. W. and Thompson, E. A. (1992). Performing the exact test of Hardy-Weinberg proportion for multiple alleles, Biometrics, 48, 361-372.
- Hirshhorn, J. N., Lohmueller, K., Byrne, E. and Hirshchhorn, K. (2002). A comprehensive review of genetic association studies, Genetics in Medicine, 4, 45-61.
- Ho, G. Y. F. and Bailey-Wilson, J. E. (2000). The transmission/disequilibrium test for linkage on the X chromosome, American Journal of Human Genetics, 66, 1158-1160.
- Horvath, S. and Laird, N. M. (1998). A discordant-sibship test for disequilibrium and linkage: No need for parental data, American Journal of Human Genetics, 63, 1886-1897.
- Horvath, S., Laird, N. M. and Knapp, M. (2000). The transmission/disequilibrium test and parental-genotype reconstruction for X-chromosomal markers, American Journal of Human Genetics, 66, 1161-1167.
- Horvath, S., Xu, X., Lake, S. L., Silverman, E. K., Weiss, S. T. and Laird, N. M. (2004). Family based tests for association haplotypes with general phenotype data: Application to athma genetics, Genetic Epidemiology, 26, 61-69.
- Knapp, M. (1999). The transmission/disequilibrium test and parental-genotype reconstruction: The reconstruction-combined transmission/disequilibrium test, American Journal of Human Genetics, 64, 861-870.
- Laird, N. M. (2009). Family-based association tests and the FBAT-toolkit user's manual (updated march 2009), Harvard school of public health, Boston, MA.
- Laird, N. M. and Lange, C. (2008). Family-based methods for linkage and association analysis, Advances in genetics, 60, 219-252.
- Lake, S., Silverman, E., Weiss, S., Laird, N. and Schaid, D. J. (2003). Estimation and tests of haplotype environment interaction when linkage phase is ambiguous, Human Heredity, 55, 56-65.
- Lange, C., Silverman, E. K., Xu, X., Weiss, S. T. and Laird, N. M. (2003). A multivariate family-based association test using generalized estimating equations: FBAT-GEE, Biostatistics, 4, 195-206.
- Lunetta, K., Faraone, S. V., Biederman, J. and Laird, N. M. (2000). Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions, American Journal of Human Genetics, 66, 605-614.
- Martin, E. R., Monks, S. A., Warren, L. L. and Kaplan, N. L. (2000). A test for linkage and association in general pedigrees: The pedigree disequilibrium test, American Journal of Human Genetics, 67, 146-154.
- Monks, S. A. and Kaplan, N. L. (2000). Removing the sampling restrictions from family-based tests of association for a quantitative-trait locus, American Journal of Human Genetics, 66, 576-592.
- Monks, S. A., Kaplan, N. L. and Weir, B. S. (1998). A comparative study of sibship tests of linkage and/or association, American Journal of Human Genetics, 63, 1507-1516.
- Rakovski, C., Xu, X., Lazaras, R. and Laird, N. (2007). A new multimarker test for family-based association studies, Genetic Epidemiology, 31, 9-17.
- Rice, J. P., Neuman, R. J., Hoshaw, S. L., Daw, E. W. and Gu, C. (1995). TDT with covariates and genomic screens with mod scores: their behavior on simulated data, Genetic Epidemiology, 12, 659-664.
- Risch, N. and Merikangas, K. (1996). The future of genetic studies of complex human diseases, Science, 273, 1516-1517.
- Saito, Y. A., Talley, N., Andrade, M. and Petewrsen, G. (2006). Case-control genetic association studies in gastrointestinal disease: Review and recommendations, American Journal of Gastrointorology, 101, 1379-1389.
- SAS Institute. (2005). SAS Genetics 9.1.3 User's Guide, SAS Institute, Inc. Cary, NC.
- Schaid, D. J., Rowland, C. M., Tines, D. E., Jacobson, R. M. and Poland, G. A. (2002). Score tests for association between traits and haplotypes when linkage phase is ambiguous, American Journal of Human Genetics, 70, 425-434.
- Scheet, P. and Stephens, M. (2006). A fast and flexible statistical model for large-scale population genotype data: Applications to inferring missing genotypes and haplotypic phase, American Journal of Human Genetics, 78, 629-644.
- Sham, P. C. (1998). Statistics in Human Genetics, Arnold.
- Slager, S. L. and Schaid, D. J. (2001). Evaluation of candidate genes in case-control studies: A statistical method to account for related subjects, American Journal of Human Genetics, 68, 1457-1462.
- Spielman, R. S. and Ewens, W. J. (1996). The TDT and other family-based tests for linkage disequilibrium and association, American Journal of Human Genetics, 59, 983-989.
- Spielman, R. S. and Ewens, W. J. (1998). A sibship test for linkage in the presence of association: The sib transmission/disequilibrium test, American Journal of Human Genetics, 62, 450-458.
- Stephens, M., Smith, N. J. and Donnelly, P. (2001). A new statistical method for haplotype reconstruction from population data, American Journal of Human Genetics, 68, 978-989.
- Xie, R. and Stram, D. O. (2005). Asymptotic equivalence between two score tests for haplotype-specific risk in general linear models, Genetic Epidemiology, 29, 166-170.
- Xu, H. and George, V. (2007). A new transmission test for affected sib-pair families, BMC Proceedings, 1(Suppl 1), S32.
- Zaykin, D. V., Westfall, P. H., Young, S. S., Karnoub, M. A., Wagner, M. J. and Ehm, M. G. (2002). Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals, Human Heredity, 53, 79-91.
- Zhao, H. (2000). Family-based association studies, Statistical Methods in Medical Research, 9, 563-587.
- Zhao, H., Zhang S., Merikangas, K. R., Wildenaur, D., Sun, F. and Kidd, K. K. (2000). Transmission/disequilibrium test for multiple tightly linked markers, American Journal of Human Genetics, 67, 936-946.
- Zhu, X. and Elston, R. C. (2001). Transmission/disequilibrium test for quantitative traits, Genetic Epidemiology, 20, 57-74.
이 논문을 인용한 문헌 (2)
- Jung, Ji-Won ; Lee, Suk-Hoon ; Kim, Soon-Ae ; Park, Mi-Ra 2010. "Comparison of Genetic Association Analyses Using Sib Information in Family-Based Study" 한국통계학회 논문집 = Communications of the Korean Statistical Society, 17(5): 733~743
- 2012. "" 응용통계연구 = The Korean journal of applied statistics, 25(4): 563~573
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