Genomewide search for type 2 diabetes mellitus susceptibility loci in Finnish families: The Botnia study

Lindgren, CM; Mahtani, MM; Widen, E; McCarthy, MI; Daly, MJ; Kirby, A; Reeve, MP; Kruglyak, L; Parker, A; Meyer, J; Almgren, P; Lehto, M; Kanninen, T; Tuomi, T; Groop, LC; Lander, ES

Author(s): Lindgren, CM; Mahtani, MM; Widen, E; McCarthy, MI; Daly, MJ; Kirby, A; Reeve, MP; Kruglyak, L; Parker, A; Meyer, J; Almgren, P; Lehto, M; Kanninen, T; Tuomi, T; Groop, LC; Lander, ES;
Details: Publication Year 2002-02,Volume 70,Issue #2,Page 509-516
Journal Title: AMERICAN JOURNAL OF HUMAN GENETICS
Publication Type: Journal Article
Abstract: Type 2 diabetes mellitus is a heterogeneous inherited disorder characterized by chronic hyperglycemia resulting from pancreatic beta-cell dysfunction and insulin resistance. Although the pathogenic mechanisms are not fully understood, manifestation of the disease most likely requires interaction between both environmental and genetic factors. In the search for such susceptibility genes, we have performed a genomewide scan in 58 multiplex families (comprising 440 individuals, 229 of whom were affected) from the Botnia region in Finland. Initially, linkage between chromosome 12q24 and impaired insulin secretion had been reported, by Mahtani et al., in a subsample of 26 families. In the present study, we extend the initial genomewide scan to include 32 additional families, update the affectation status, and fine map regions of interest, and we try to replicate the initial stratification analysis. In our analysis of all 58 families, we identified suggestive linkage to one region, chromosome 9p13-q21 (nonparametric linkage [NPL] score 3.9; P < .0002). Regions with nominal P values <.05 include chromosomes 2p11 (NPL score 2.0 [P<.03]), 3p24-p22 (NPL score 2.2 [P<.02]), 4q32-q33 (NPL score 2.5 [P<.01]), 12q24 (NPL score [P<.03]), 16p12-11 (NPL score 1.7 [P<.05]), and 17p12-p11 (NPL score 1.9 [P<.03]). When chromosome 12q24 was analyzed in only the 32 additional families, a nominal P value <.04 was observed. Together with data from other published genomewide scans, these findings lend support to the hypothesis that regions on chromosome 9p13-q21 and 12q24 may harbor susceptibility genes for type 2 diabetes.
Publisher: UNIV CHICAGO PRESS
Keywords: AUTOSOMAL GENOMIC SCAN; PIMA-INDIANS; MEXICAN-AMERICANS; LINKAGE ANALYSIS; CHROMOSOME 12Q; COMPLEX TRAITS; MAPPING GENES; WIDE SEARCH; ONSET; NIDDM
Publisher's Version: https://doi.org/10.1086/338629
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-02-01 12:00:00