Genetic Epidemiology


Video Lectures

Introductory papers to genetic association studies

  • Lewis CM. Genetic association studies: design, analysis and interpretation. Brief Bioinform. 2002 Jun;3(2):146-53. [PDF]
  • Balding DJ. A tutorial on statistical methods for population association studies.Nat Rev Genet. 2006;7(10):781-91. [PDF]
  • Sasieni PD (1997) From genotypes to genes: doubling the sample size. Biometrics 53(4): 1253-1261 [PDF]
  • Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K (2002) A comprehensive review of genetic association studies. Genet Med 4(2): 45-61
  • Li W. Three lectures on case-control genetic association analysis. Brief Bioinform. 2008 Jan;9(1):1-13. [PDF]
  • Elston RC, Spence MA. Advances in statistical human genetics over the last 25 years. Stat Med 2006; 25:3049–3080 [PDF]
  • Brookfield JF.Q&A: promise and pitfalls of genome-wide association studies.BMC Biol. 2010;8:41.[PDF]

A series of review papers for genetic epidemiology published in Lancet

  • Burton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet. 2005;366(9489):941-51.[PDF]
  • Dawn Teare M, Barrett JH. Genetic linkage studies.Lancet. 2005;366(9490):1036-44.[PDF]
  • Cordell HJ, Clayton DG. Genetic association studies. Lancet. 2005;366(9491):1121-31. [PDF]
  • Palmer LJ, Cardon LR. Shaking the tree: mapping complex disease genes with linkage disequilibrium.Lancet. 2005;366(9492):1223-34. [PDF]
  • Hattersley AT, McCarthy MI. What makes a good genetic association study? Lancet. 2005;366(9493):1315-23. [PDF]
  • Hopper JL, Bishop DT, Easton DF. Population-based family studies in genetic epidemiology.Lancet. 2005;366(9494):1397-406. [PDF]

Important papers for special topics in genetic association studies

Family-based association studies

  • Terwilliger JD, Ott J (1992) A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. Hum Hered 42(6): 337-346
  • Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52(3): 506-516 [PDF]
  • Spielman RS, Ewens WJ (1996) The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 59(5): 983-989 [PDF]
  • Whittaker JC, Morris AP (2001) Family-based tests of association and/or linkage. Ann Hum Genet 65(Pt 5): 407-419
  • D. J. Schaid and S. S. Sommer. Comparison of statistics for candidate-gene association studies using cases and parents. Am J Hum Genet. 1994 August; 55(2): 402–409 [PDF]
  • Evangelou E, Trikalinos TA, Salanti G, Ioannidis JP (2006) Family-based versus unrelated case-control designs for genetic associations. PLoS Genet 2(8): e123 [PDF]

Haplotype analysis

  • Xu H, Wu X, Spitz MR, Shete S (2004) Comparison of haplotype inference methods using genotypic data from unrelated individuals. Hum Hered 58(2): 63-68 [PDF]
  • Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68(4): 978-989 [PDF]
  • Schaid DJ (2004) Evaluating associations of haplotypes with traits. Genet Epidemiol 27(4): 348-364
  • Liu N, Zhang K, Zhao H (2008) Haplotype-association analysis. Adv Genet 60: 335-405

Hardy-Weinberg equilibrium

  • Trikalinos TA, Salanti G, Khoury MJ, Ioannidis JP (2006) Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations. Am J Epidemiol 163(4): 300-309 [PDF]
  • Pereira C, Rogatko A (1984) The Hardy-Weinberg equilibrium under a Bayesian perspective. Rev  Bras Genet 4: 689–707
  • Shoemaker J, Painter I, Weir BS.A Bayesian characterization of Hardy-Weinberg disequilibrium.Genetics. 1998;149(4):2079-88.[PDF]
  • Hernandez JL, Weir BS (1989) A disequilibrium coefficient approach to Hardy-Weinberg testing. Biometrics 45(1): 53-70
  • Lindley D (1988) Statistical inference concerning Hardy-Weinberg equilibrium. Bayesian Stat 3: 307–326

Linkage Disequilibrium

  • Zondervan KT, Cardon LR (2004) The complex interplay among factors that influence allelic association. Nat Rev Genet 5(2): 89-100
  • Pritchard JK, Przeworski M (2001) Linkage disequilibrium in humans: models and data. Am J Hum Genet 69(1): 1-14 [PDF]
  • Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39(7): 906-913 [PDF]
  • Guo SW (1997) Linkage disequilibrium measures for fine-scale mapping: a comparison. Hum Hered 47(6): 301-314
  • Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55(4): 997-1004
  • Devlin B, Risch N. A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics. 1995; 20;29(2):311-22. [PDF]
  • Cardon LR, Palmer LJ (2003) Population stratification and spurious allelic association. Lancet 361(9357): 598-604

Gene-gene and gene-environment interactions

  • Begg CB, Zhang ZF: Statistical analysis of molecular epidemiology studies employing case-series. Cancer Epidemiology Biomarkers & Prevention 1994, 3:173 -175. [PDF]
  • Khoury MJ, Flanders WD: Nontraditional Epidemiologic Approaches in the Analysis of Gene Environment Interaction: Case-Control Studies with No Controls! American Journal of Epidemiology 1996, 144:207 -213. [PDF]
  • Umbach DM, Weinberg CR: Designing and analysing case-control studies to exploit independence of genotype and exposure. Stat Med 1997, 16:1731-1743.
  • Schmidt S, Schaid DJ: Potential Misinterpretation of the Case-Only Study to Assess Gene-Environment Interaction. American Journal of Epidemiology 1999, 150:878 -885. [PDF]
  • Yang Q, Khoury MJ, Sun F, Flanders WD: Case-only design to measure gene-gene interaction. Epidemiology 1999, 10:167-170.
  • Andrieu N, Goldstein AM: Epidemiologic and genetic approaches in the study of gene-environment interaction: an overview of available methods. Epidemiol Rev 1998, 20:137-147.[PDF]
  • Cortina-Borja M, Smith AD, Combarros O, Lehmann DJ: The synergy factor: a statistic to measure interactions in complex diseases. BMC Res Notes , 2:105-105. [PDF]

Methodological papers for meta-analysis of genetic association studies

  • Munafo MR, Flint J. Meta-analysis of genetic association studies (2004). Trends in Genetics, 20(9): 439-444 [PDF]
  • Thakkinstian A, McElduff P, D'Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9): 1291-1306
  • Bagos PG.A unification of multivariate methods for meta-analysis of genetic association studies. 2008, Statistical Applications in Genetics and Molecular Biology, 7(1), Article 13 [PDF]
  • Minelli C, Thompson JR, Abrams KR, Thakkinstian A, Attia J (2005) The choice of a genetic model in the meta-analysis of molecular association studies. Int J Epidemiol 34(6): 1319-1328 [PDF]
  • Minelli C, Thompson JR, Abrams KR, Lambert PC (2005) Bayesian implementation of a genetic model-free approach to the meta-analysis of genetic association studies. Stat Med 24(24): 3845-3861
  • Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27(8): 1133-1163
  • Minelli C, Thompson JR, Tobin MD, Abrams KR (2004) An integrated approach to the meta-analysis of genetic association studies using Mendelian randomization. Am J Epidemiol 160(5): 445-452 [PDF]
  • Thompson JR, Minelli C, Abrams KR, Tobin MD, Riley RD (2005) Meta-analysis of genetic studies using Mendelian randomization--a multivariate approach. Stat Med 24(14): 2241-2254
  • Palmer TM, Thompson JR, Tobin MD (2008) Meta-analysis of Mendelian randomization studies incorporating all three genotypes. Stat Med 27(30): 6570-6582
  • Verzilli C, Shah T, Casas JP, Chapman J, Sandhu M, Debenham SL, Boekholdt MS, Khaw KT, Wareham NJ, Judson R, Benjamin EJ, Kathiresan S, Larson MG, Rong J, Sofat R, Humphries SE, Smeeth L, Cavalleri G, Whittaker JC, Hingorani AD (2008) Bayesian meta-analysis of genetic association studies with different sets of markers. Am J Hum Genet 82(4): 859-872 [PDF]
  • Newcombe PJ, Verzilli C, Casas JP, Hingorani AD, Smeeth L, Whittaker JC (2009) Multilocus Bayesian meta-analysis of gene-disease associations. Am J Hum Genet 84(5): 567-580 [PDF]
  • Bagos PG, Liakopoulos TD. A multipoint method for meta-analysis of genetic association studies. 2010, Genetic Epidemiology, 34(7):702-15 [PDF]
  • Salanti G, Higgins JP, White IR (2006) Bayesian synthesis of epidemiological evidence with different combinations of exposure groups: application to a gene-gene-environment interaction. Stat Med 25(24): 4147-4163
  • Salanti G, Higgins JP, Trikalinos TA, Ioannidis JP (2007) Bayesian meta-analysis and meta-regression for gene-disease associations and deviations from Hardy-Weinberg equilibrium. Stat Med 26(3): 553-567
  • Salanti G, Higgins JP (2008) Meta-analysis of genetic association studies under different inheritance models using data reported as merged genotypes. Stat Med 27(5): 764-777
  • Hong F, Breitling R (2008) A comparison of meta-analysis methods for detecting differentially expressed genes in microarray experiments. Bioinformatics 24(3): 374-382 [PDF]
  • Sagoo GS, Little J, Higgins JPT, 2009 Systematic Reviews of Genetic Association Studies. PLoS Med 6(3): e1000028. [PDF]
  • Zeggini E, Ioannidis JP: Meta-analysis in genome-wide association studies. Pharmacogenomics 2009, 10:191-201. [PDF
  • Lin DY, Zeng D: Meta-analysis of genome-wide association studies: no efficiency gain in using individual participant data. Genet. Epidemiol 2010, 34:60-66. 
  • Willer CJ, Li Y, Abecasis GR: METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 2010, 26:2190-2191.[PDF
  • Lin D, Sullivan PF: Meta-Analysis of Genome-wide Association Studies with Overlapping Subjects. Am J Hum Genet 2009, 85:862-872.  [PDF]