Confounding, ascertainment bias, and the blind quest for a genetic 'fountain of youth'

Annals of Medicine

Volumn 35, Issue 7, 2003, Pages 532-544

  Terwilliger, Joseph D ^a,b   Weiss, Kenneth M ^b,c  

^a NEW YORK STATE PSYCHIATRIC INSTITUTE   (United States)

^b Pennsylvania State University ^*  (United States)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

Ascertainment bias; Confounding; Gene mapping; Genetic epidemiology; Linkage analysis; Linkage disequilibrium

Indexed keywords

EPIDEMIOLOGICAL DATA; EXPOSURE; GENE IDENTIFICATION; GENE MAPPING; GENETIC ANALYSIS; GENETIC LINKAGE; GENETIC RISK; GENETIC TRAIT; GENETIC VARIABILITY; HEALTH CARE POLICY; MEDICAL DECISION MAKING; MEDICAL PRACTICE; PRIORITY JOURNAL; PROGNOSIS; PUBLIC HEALTH; REVIEW; SCIENCE; STOCHASTIC MODEL;

ANIMALS; ENVIRONMENTAL EXPOSURE; EPIDEMIOLOGY; GENETIC RESEARCH; GENETICS; GENETICS, MEDICAL; HUMANS; LINKAGE (GENETICS); LINKAGE DISEQUILIBRIUM; MODELS, ANIMAL; MOLECULAR BIOLOGY; PUBLIC HEALTH; STOCHASTIC PROCESSES; VARIATION (GENETICS);

EID: 0242660361     PISSN: 07853890     EISSN: None     Source Type: Journal    
DOI: 10.1080/07853890310015181     Document Type: Review

References (58)

1. Collins FS. Genetics: An explosion of knowledge is transforming clinical practice. Geriatrics 1999;54:41-7.
2. Collins FS. Shattuck lecture -Medical and societal consequences of the human genome project. N Engl J Med 1999;341: 28-37.
3. Begg CB. On the use of familial aggregation in population-based case probands for calculating penetrance. J Natl Cancer Inst 2002;94:1221-6.
4. Welsch PL, King MC. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet 2001;10:705-13.
5. Weiss K. Goings on in Mendel's Garden. Evol Anthropol 2002;11:40-4.
6. Collins FS. Evolution of a vision: Genome project origins, present and future challenges, and far-reaching benefits. Hum Genome News 1995;7:2.
7. Collins FS. The human Genome Project and the future of medicine. Great Issues for Medicine in the Twenty-First Century. New York: New York Acad Sciences; 1999:42-55.
8. Perheentupa J. The Finnish disease heritage: a personal look. Acta Paediatrica 1995;84:1094-9.
9. Peltonen L, Pekkarinen P, Aaltonen J. Messages from an isolate: lessons from the Finnish gene pool. Biol Chem Hoppe-Seyler 1995;376:697-704.
10. Peltonen L. Molecular background of the Finnish disease heritage. Ann Med 1997;29:553-6.
11. Peltonen L, Jalanko A, Varilo T. Molecular genetics of the Finnish disease heritage. Hum Mol Genet 1999;8:1913-23.
12. Kreutz R, Hubner N. Congenic rat strains are important tools for the genetic dissection of essential hypertension. Semin Nephrol 2002;22:135-47.
13. Kwitek-Black AE, Jacob HJ. The use of designer rats in the genetic dissection of hypertension. Curr Hypertens Rep 2001; 3:12-8.
14. Todd JA. From genome to aetiology in a multifactorial disease, type 1 diabetes. Bioessays 1999;21:164-74.
15. Cicila GT, Lee SJ. Identifying candidate genes for blood pressure quantitative trait loci using differential gene expression and a panel of congenic strains. Hypertens Res 1998;21: 289-96.
16. Montagutelli X. Effect of the genetic background on the phenotype of mouse mutations. J Am Soc Nephrol 2000;11: S101-5.
17. Weiss KM, Terwilliger JD. How many diseases does it take to map a gene with SNPs? Nat Genet 2000;26:151-7.
18. Terwilliger JD, Goring HHH. Gene mapping in the 20th and 21st centuries: Statistical methods, data analysis, and experimental design. Hum Biol 2000;72:63-132.
19. Terwilliger JD, Weiss KM. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol 1998;9:578-94.
20. Weiss KM. Is there a paradigm shift in genetics? Lessons from the study of human diseases. Mol Phylogenet Evol 1996;5:259-65.
21. Weiss KM. Genetic Variation and Human Disease: Principles and evolutionary approaches. Cambridge: Cambridge University Press; 1993.
22. Weiss KM. In search of human variation. Genome Res 1998;8: 691-7.
23. Patterson M. That damned elusive polygene. Nat Rev Genet 2000;1:86.
24. Patterson M. Wake-up call for genome scanners. Nat Rev Genet 2002;3:9.
25. Millikan R. The Changing Face of Epidemiology in the Genomics Era. Epidemiology 2002;13:472-80.
26. Holtzman NA. Putting the search for genes in perspective. Int J Health Serv 2001;31:445-61.
27. Horrobin DE. Realism in drug discovery - could Cassandra he right? Nat Biotechnol 2001;19:1099-100.
28. Kulldorff M, Feuer EJ, Miller BA, Freedman LS. Breast cancer clusters in the northeast United States: a geographic analysis. Am J Epidemiol 1997;146:161-70.
29. Merkin SS, Stevenson L, Powe N. Geographic socioeconomic status, race, and advanced-stage breast cancer in New York City. Am J Public Health 2002;92:64-70.
30. Neel JV. Diabetes mellitus: a "thrifty genotype" rendered detrimental by "progress". Am J Hum Genet 1962;14:353-62.
31. Neel JV. The thrifty genotype revisited. In: Kobberling J, Tattersall R, Eds. The Genetics of Diabetes Mellitus. New York: John Wiley; 1982.
32. Terwilliger JD, Haghighi F, Hiekkalinna TS, Goring HH. A biased assessment of the use of SNPs in human complex traits. Curr Opin Genet Dev 2002;12:726-34.
33. Goring HHH, Terwilliger JD, Blangero J. Large upward bias in estimation of locus-specific effects from genome-wide scans. Am J Hum Genet 2001;69:1357-69.
34. Goring HHH, Terwilliger JD, Blangero J. Genome scans for quantitative trait loci using variance components linkage analysis: upward bias in heritability estimates attributable to individual quantitative trait loci at lod score peaks. Am J Hum Genet 2000;67:1176.
35. Weiss KM, Clark AG, Fullerton SM, Taylor SL, Nickerson DA, Sing CF. Evaluating the phenotypic effects of SNP variation: sampling issues. Am J Hum Genet 1999;65:8.
36. Terwilliger JD, Goring HHH, Magnusson PKE, Lee JH. Study design for genetic epidemiology and gene mapping: The Korean diaspora project. Shengming Kexue Yanjiu (Life Science Research) 2002;6:95-115.
37. Weiss KM, Fullerton SM. Phenogenetic drift and the evolution of genotype-phenotype relationships. Theor Popul Biol 2000; 57:187-95.
38. Terwilliger JD. On the resolution and feasiblity of genome scanning approaches. Adv Genet 2001;42:351-91.
39. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I. Identification of a variant associated with adult-type hypolactasia. Nat Genet 2002;30:233-7.
40. Pekkarinen P, Kestila M, Paloneva J, Terwilliger J, Varilo T, Jarvi O, et al. Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium. Genomics 1998;54:307-15.
41. Nikali K, Suomalainen A, Terwilliger J, Koskinen T, Weissenbach J, Peltonen L. Random Search for Shared Chromosomal Regions in 4 Affected Individuals - the Assignment of a New Hereditary Ataxia Locus. Am J Hum Genet 1995;56:88-1095.
42. Haberhausen G, Schmitt I, Kohler A, Peters U, Rider S, Chelly J, et al. Assignment of the Dystonia-Parkinsonism Syndrome Locus, Dyt3, to a Small Region within a 1.8-Mb Yac Contig of Xq13.1. Am J Hum Genet 1995;57:644-50.
43. Rahachowdhury R, Bowen DJ, Stone C, Pointon JJ, Terwilliger JD, Shearman JD, et al. New Polymorphic Microsatellite Markers Place the Hemochromatosis Gene Telomeric to D6s105. Hum Mol Genet 1995;4:1869-74.
44. Norio R. [The future of the hereditary diseases in Finland]. Duodecim 1994;110:640-3.
45. Norio R, Nevanlinna HR, Perheentupa J. Hereditary diseases in Finland: rare flora in rare soul. Ann Clin Res 1973;5:109-41.
46. Nevanlinna HR. [Finnish population as an object of epidemiological studies]. Duodecim 1974;90:1548-53.
47. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome. Science 2002;296:2225-9.
48. Judson R, Salisbury B, Schneider J, Windemuth A, Stephens JC. How many SNPs does a genome-wide haplotype map require? Pharmacogenomics 2002;3:379-91.
49. Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES. Fine-structure haplotype map of 5q31: implications for gene-based association studies and genomic LD mapping. Am J Hum Genet 2001;69:28.
50. Daly MJ, Rioux JD, Schaffner SE, Hudson TJ, Lander ES. High-resolution haplotype structure in the human genome. Nat Genet 2001;29:229-32.
51. Weiss KM, Clark AG. Linkage disequilibrium and the mapping of complex human traits. Trends Genet 2002;18:19-24.
52. Proctor RN. Cancer Wars. New York: Basic Books; 1995.
53. Kondrashov AS. Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum Mutat 2003;21:12-27.
54. Mackay TFC. The genetic architecture of quantitative traits. Annu Rev Genet 2001;35:303-339.
55. Weiss KM, Buchanan AV. Evolution by phenotype: a biomedical perspective. Perspect Biol Med 2003;46:159-82.
56. Kohler RE. Lords of the fly: Drosophila genetics and the experimental life. Chicago: University of Chicago Press; 1994.
57. Silver LM. Mouse genetics: concepts and applications. New York: Oxford University Press; 1995.
58. Guyer MS, Collins FS. The Human Genome Project and the Future of Medicine. Am J Dis Child 1993;147:1145-52.