The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes

Abstract

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.

A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study

“…In a genome scan in 719 Finnish sib-pairs with Type 2 diabetes an MLS of 1.75 was found in exactly the same region on chromosome 11 (84 cM) [41]. In a QTL analysis in the same population, however, this region has not been replicated [6].…”

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

“…The chance of incorrect assignment due to inheritance inconsistency is small because these families were previously typed for >400 microsatellites spanning the nuclear genome and inconsistent families were removed (Ghosh et al 2000;Silander et al 2004). 4452 7309 8271 4769 4529 10238 12612 13708 15607 13368 12308 11467 9055 1189 4646 5999 9477 13617 14793 13827 5656 10927 5240 6392 15904 4580 8994 7864 6371 8701 Reference Haplogenotype patterns observed in this study that indicate recurrent mutation or that resolve the order in which variants arose…”

Analysis of the contribution to type 2 diabetes susceptibility of sequence variation in the gene encoding stearoyl-CoA desaturase, a key regulator of lipid and carbohydrate metabolism

“…Evidence for linkage to type 2 diabetes at chromosome 10q has been reported in several studies [18,19,20,21,22], including the UK Warren 2 study, where a LOD of 1.99 was found at D10S1765 (approximately 12 Mb pter to SCD on the current genome assembly [NCBI version 34, accessed at www.ensembl.org, 23 September, 2004]). This is the first study to test the hypothesis that SCD variation contributes to type 2 diabetes susceptibility.…”