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Multicenter Study
. 2000 Nov;67(5):1186-200.
Epub 2000 Oct 13.

The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci

R M Watanabe  1 , S Ghosh, C D Langefeld, T T Valle, E R Hauser, V L Magnuson, K L Mohlke, K Silander, D S Ally, P Chines, J Blaschak-Harvan, J A Douglas, W L Duren, M P Epstein, T E Fingerlin, H S Kaleta, E M Lange, C Li, R C McEachin, H M Stringham, E Trager, P P White, J Balow Jr, G Birznieks, J Chang, W Eldridge
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Multicenter Study

The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci

R M Watanabe et al. Am J Hum Genet. 2000 Nov.

Abstract

Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

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Figures

Figure 1
Figure 1
A, MLS curves for age-, sex-, and BMI-adjusted IRC and for age-, sex-, and BMI-adjusted fasting C-peptide, for chromosome 3 in diabetic subjects. B, MLS curves for results for chromosome 13 in diabetic subjects. Unadjusted BMI showed the strongest evidence for linkage. However, a cluster of other traits—fasting insulin; SI(EST); and age-, sex-, and WHR-adjusted fasting C-peptide—showed weaker evidence for linkage at a different locus. Marker names and positions are given at the top of each graph.
Figure 2
Figure 2
A, MLS curves for age-, sex-, and BMI-adjusted AIR and for fasting glucose, for chromosome 10 in nondiabetic subjects. B, MLS curves for age- and sex-adjusted 2-h insulin and for age-, sex-, and BMI-adjusted IRI, for chromosome 13 in nondiabetic subjects. C, MLS curves for age- and sex-adjusted IRI, age- and sex-adjusted fasting insulin, for age-, sex-, and BMI-adjusted 2-h insulin, and for age- and sex-adjusted SI(EST), for chromosome 17 in nondiabetic subjects.
Figure 3
Figure 3
A, MLS curves for age- and sex-adjusted BMI in diabetic subjects and for BMI in nondiabetic subjects, for chromosome 3. When data from both groups are analyzed jointly, BMI shows a strong signal at 59.5 cM, with an MLS of 3.43. B, MLS curves for age-, sex-, and BMI-adjusted SI(EST) in diabetic subjects and for age- and sex-adjusted SI(EST) in nondiabetic subjects, for chromosome 17. Joint analysis of age-, sex-, and BMI-adjusted SI(EST) shows a stronger signal (MLS = 3.61) at the p-terminus. C, MLS curves for age- and sex-adjusted SI(EST), in both diabetic and nondiabetic subjects, for chromosome 19. Joint analysis of age-, sex-, and WHR-adjusted SI(EST) shows a stronger signal (MLS = 2.80) at 74.5 cM.
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References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www3.ncbi.nlm.nih.gov/Omim (for PPARG [MIM 601487], SST [MIM 182450], TNF [MIM 191160], GLP1R [MIM 138032], FBP1 [MIM 229700], FBP2 [MIM 603027], CKM [MIM 123310], GIPR [MIM 137241], HNF3G [MIM 602295], GYS1 [MIM 138570], PK1 [MIM 266200], KCNJ9 [MIM 600932], IGFBP1 [MIM 146730], IGFBP3 [MIM 146732], GCK [MIM 138079], PCK2 [MIM 261650], HNF3A [MIM 602294], SLC2A4 [MIM 138190], MAP2K4 [MIM 601335], and ADORA2B [MIM 600446])

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