A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter (original) (raw)

Abstract

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score </= -2) for lambdas >/= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

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Selected References

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  1. Bishop D. T., Williamson J. A. The power of identity-by-state methods for linkage analysis. Am J Hum Genet. 1990 Feb;46(2):254–265. [PMC free article] [PubMed] [Google Scholar]
  2. Boehnke M. Allele frequency estimation from data on relatives. Am J Hum Genet. 1991 Jan;48(1):22–25. [PMC free article] [PubMed] [Google Scholar]
  3. Boehnke M., Cox N. J. Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet. 1997 Aug;61(2):423–429. doi: 10.1086/514862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cerasi E., Ependić S., Luft R. Dose-response relation between plasma-insulin and blood-glucose levels during oral glucose loads in prediabetic and diabetic subjects. Lancet. 1973 Apr 14;1(7807):794–797. doi: 10.1016/s0140-6736(73)90599-0. [DOI] [PubMed] [Google Scholar]
  5. Dausset J., Cann H., Cohen D., Lathrop M., Lalouel J. M., White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990 Mar;6(3):575–577. doi: 10.1016/0888-7543(90)90491-c. [DOI] [PubMed] [Google Scholar]
  6. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  7. Eriksson J., Franssila-Kallunki A., Ekstrand A., Saloranta C., Widén E., Schalin C., Groop L. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989 Aug 10;321(6):337–343. doi: 10.1056/NEJM198908103210601. [DOI] [PubMed] [Google Scholar]
  8. Ghosh S., Karanjawala Z. E., Hauser E. R., Ally D., Knapp J. I., Rayman J. B., Musick A., Tannenbaum J., Te C., Shapiro S. Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group. Genome Res. 1997 Feb;7(2):165–178. doi: 10.1101/gr.7.2.165. [DOI] [PubMed] [Google Scholar]
  9. Ghosh S., Schork N. J. Genetic analysis of NIDDM. The study of quantitative traits. Diabetes. 1996 Jan;45(1):1–14. doi: 10.2337/diab.45.1.1. [DOI] [PubMed] [Google Scholar]
  10. Haffner S. M., Miettinen H., Stern M. P. Insulin secretion and resistance in nondiabetic Mexican Americans and non-Hispanic whites with a parental history of diabetes. J Clin Endocrinol Metab. 1996 May;81(5):1846–1851. doi: 10.1210/jcem.81.5.8626845. [DOI] [PubMed] [Google Scholar]
  11. Hani E. H., Hager J., Philippi A., Demenais F., Froguel P., Vionnet N. Mapping NIDDM susceptibility loci in French families: studies with markers in the region of NIDDM1 on chromosome 2q. Diabetes. 1997 Jul;46(7):1225–1226. doi: 10.2337/diab.46.7.1225. [DOI] [PubMed] [Google Scholar]
  12. Hanis C. L., Boerwinkle E., Chakraborty R., Ellsworth D. L., Concannon P., Stirling B., Morrison V. A., Wapelhorst B., Spielman R. S., Gogolin-Ewens K. J. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet. 1996 Jun;13(2):161–166. doi: 10.1038/ng0696-161. [DOI] [PubMed] [Google Scholar]
  13. Hauser E. R., Boehnke M., Guo S. W., Risch N. Affected-sib-pair interval mapping and exclusion for complex genetic traits: sampling considerations. Genet Epidemiol. 1996;13(2):117–137. doi: 10.1002/(SICI)1098-2272(1996)13:2<117::AID-GEPI1>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  14. Holmans P. Asymptotic properties of affected-sib-pair linkage analysis. Am J Hum Genet. 1993 Feb;52(2):362–374. [PMC free article] [PubMed] [Google Scholar]
  15. Kaprio J., Tuomilehto J., Koskenvuo M., Romanov K., Reunanen A., Eriksson J., Stengård J., Kesäniemi Y. A. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia. 1992 Nov;35(11):1060–1067. doi: 10.1007/BF02221682. [DOI] [PubMed] [Google Scholar]
  16. Kruglyak L., Daly M. J., Reeve-Daly M. P., Lander E. S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996 Jun;58(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
  17. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  19. Lange K., Weeks D., Boehnke M. Programs for Pedigree Analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol. 1988;5(6):471–472. doi: 10.1002/gepi.1370050611. [DOI] [PubMed] [Google Scholar]
  20. Magnuson V. L., Ally D. S., Nylund S. J., Karanjawala Z. E., Rayman J. B., Knapp J. I., Lowe A. L., Ghosh S., Collins F. S. Substrate nucleotide-determined non-templated addition of adenine by Taq DNA polymerase: implications for PCR-based genotyping and cloning. Biotechniques. 1996 Oct;21(4):700–709. doi: 10.2144/96214rr03. [DOI] [PubMed] [Google Scholar]
  21. Mahtani M. M., Widén E., Lehto M., Thomas J., McCarthy M., Brayer J., Bryant B., Chan G., Daly M., Forsblom C. Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families. Nat Genet. 1996 Sep;14(1):90–94. doi: 10.1038/ng0996-90. [DOI] [PubMed] [Google Scholar]
  22. Risch N., Giuffra L. Model misspecification and multipoint linkage analysis. Hum Hered. 1992;42(1):77–92. doi: 10.1159/000154047. [DOI] [PubMed] [Google Scholar]
  23. Risch N. Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):229–241. [PMC free article] [PubMed] [Google Scholar]
  24. Stern M. P., Duggirala R., Mitchell B. D., Reinhart L. J., Shivakumar S., Shipman P. A., Uresandi O. C., Benavides E., Blangero J., O'Connell P. Evidence for linkage of regions on chromosomes 6 and 11 to plasma glucose concentrations in Mexican Americans. Genome Res. 1996 Aug;6(8):724–734. doi: 10.1101/gr.6.8.724. [DOI] [PubMed] [Google Scholar]
  25. Suarez B. K., Hodge S. E. A simple method to detect linkage for rare recessive diseases: an application to juvenile diabetes. Clin Genet. 1979 Feb;15(2):126–136. doi: 10.1111/j.1399-0004.1979.tb01751.x. [DOI] [PubMed] [Google Scholar]
  26. Tuomilehto J., Korhonen H. J., Kartovaara L., Salomaa V., Stengård J. H., Pitkänen M., Aro A., Javela K., Uusitupa M., Pitkäniemi J. Prevalence of diabetes mellitus and impaired glucose tolerance in the middle-aged population of three areas in Finland. Int J Epidemiol. 1991 Dec;20(4):1010–1017. doi: 10.1093/ije/20.4.1010. [DOI] [PubMed] [Google Scholar]
  27. Valle T., Tuomilehto J., Bergman R. N., Ghosh S., Hauser E. R., Eriksson J., Nylund S. J., Kohtamäki K., Toivanen L., Vidgren G. Mapping genes for NIDDM. Design of the Finland-United States Investigation of NIDDM Genetics (FUSION) Study. Diabetes Care. 1998 Jun;21(6):949–958. doi: 10.2337/diacare.21.6.949. [DOI] [PubMed] [Google Scholar]