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Searching for genetic determinants in the new millennium

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  • Neil J. Risch

    (Stanford University School of Medicine)

Abstract

Human genetics is now at a critical juncture. The molecular methods used successfully to identify the genes underlying rare mendelian syndromes are failing to find the numerous genes causing more common, familial, non-mendelian diseases. With the human genome sequence nearing completion, new opportunities are being presented for unravelling the complex genetic basis of non-mendelian disorders based on large-scale genome-wide studies. Considerable debate has arisen regarding the best approach to take. In this review I discuss these issues, together with suggestions for optimal post-genome strategies.

Suggested Citation

  • Neil J. Risch, 2000. "Searching for genetic determinants in the new millennium," Nature, Nature, vol. 405(6788), pages 847-856, June.
    • Handle: RePEc:nat:nature:v:405:y:2000:i:6788:d:10.1038_35015718
    DOI: 10.1038/35015718
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    Cited by:

    1. Frank, Reanne, 2007. "What to make of it? The (Re)emergence of a biological conceptualization of race in health disparities research," Social Science & Medicine, Elsevier, vol. 64(10), pages 1977-1983, May.
    2. Ding Xiao & Weiss Scott & Raby Benjamin & Lange Christoph & Laird Nan M, 2009. "Impact of Population Stratification on Family-Based Association Tests with Longitudinal Measurements," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 8(1), pages 1-19, February.
    3. Jaya M. Satagopan & E. S. Venkatraman & Colin B. Begg, 2004. "Two-Stage Designs for Gene–Disease Association Studies with Sample Size Constraints," Biometrics, The International Biometric Society, vol. 60(3), pages 589-597, September.
    4. Sirkku Karinen & Tuomas Heikkinen & Heli Nevanlinna & Sampsa Hautaniemi, 2011. "Data Integration Workflow for Search of Disease Driving Genes and Genetic Variants," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-8, April.
    5. Wanwan Tang & Xuebing Wu & Rui Jiang & Yanda Li, 2009. "Epistatic Module Detection for Case-Control Studies: A Bayesian Model with a Gibbs Sampling Strategy," PLOS Genetics, Public Library of Science, vol. 5(5), pages 1-18, May.
    6. Xiaofeng Zhu & Richard S Cooper, 2007. "Admixture Mapping Provides Evidence of Association of the VNN1 Gene with Hypertension," PLOS ONE, Public Library of Science, vol. 2(11), pages 1-10, November.
    7. Minjung Kwak & Jungnam Joo & Gang Zheng, 2009. "A Robust Test for Two-Stage Design in Genome-Wide Association Studies," Biometrics, The International Biometric Society, vol. 65(4), pages 1288-1295, December.
    8. Li, Zhaohai & Zhang, Hong & Zheng, Gang & Gastwirth, Joseph L. & Gail, Mitchell H., 2009. "Excess false positive rate caused by population stratification and disease rate heterogeneity in case-control association studies," Computational Statistics & Data Analysis, Elsevier, vol. 53(5), pages 1767-1781, March.
    9. H. Zhang & G. Zheng & Z. Li, 2006. "Statistical Analysis for Haplotype-Based Matched Case–Control Studies," Biometrics, The International Biometric Society, vol. 62(4), pages 1124-1131, December.
    10. Ning Jiang & Minghui Wang & Tianye Jia & Lin Wang & Lindsey Leach & Christine Hackett & David Marshall & Zewei Luo, 2011. "A Robust Statistical Method for Association-Based eQTL Analysis," PLOS ONE, Public Library of Science, vol. 6(8), pages 1-11, August.
    11. Kari E. North & Lisa J. Martin, 2008. "The Importance of Gene—Environment Interaction," Sociological Methods & Research, , vol. 37(2), pages 164-200, November.
    12. Jungnam Joo & Minjung Kwak & Gang Zheng, 2010. "Improving Power for Testing Genetic Association in Case–Control Studies by Reducing the Alternative Space," Biometrics, The International Biometric Society, vol. 66(1), pages 266-276, March.

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