title: 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.
authors.affiliation: Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: R M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: T T
authors.initials: TT
authors.lastname: Valle
authors.forename: E R
authors.initials: ER
authors.lastname: Hauser
authors.forename: V L
authors.initials: VL
authors.lastname: Magnuson
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: D S
authors.initials: DS
authors.lastname: Ally
authors.forename: K L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: K
authors.initials: K
authors.lastname: Silander
authors.forename: K
authors.initials: K
authors.lastname: Kohtamäki
authors.forename: P
authors.initials: P
authors.lastname: Chines
authors.forename: J
authors.initials: J
authors.lastname: Balow
authors.forename: G
authors.initials: G
authors.lastname: Birznieks
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: W
authors.initials: W
authors.lastname: Eldridge
authors.forename: M R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Z E
authors.initials: ZE
authors.lastname: Karanjawala
authors.forename: J I
authors.initials: JI
authors.lastname: Knapp
authors.forename: K
authors.initials: K
authors.lastname: Kudelko
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Morales-Mena
authors.forename: A
authors.initials: A
authors.lastname: Musick
authors.forename: T
authors.initials: T
authors.lastname: Musick
authors.forename: C
authors.initials: C
authors.lastname: Pfahl
authors.forename: R
authors.initials: R
authors.lastname: Porter
authors.forename: J B
authors.initials: JB
authors.lastname: Rayman
mesh_terms: D000368:Aged; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008297:Male; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable; D014481:United States