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Hoffmann, K.* ; Mattheisen, M.* ; Dahm, S.* ; Nürnberg, P.* ; Roe, C.* ; Johnson, J.* ; Cox, N.J.* ; Wichmann, H.-E. ; Wienker, T.F.* ; Schulze, J.* ; Schwarz, P.E.*

A German genome-wide linkage scan for type 2 diabetes supports the existence of a metabolic syndrome locus on chromosome 1p36.13 and a type 2 diabetes locus on chromosome 16p12.2.

Diabetologia 50, 418-1422 (2007)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The aim was to identify type 2 diabetes susceptibility regions in 250 German families. SUBJECTS AND METHODS: We conducted a genome-wide linkage scan using 439 short tandem repeat polymorphisms at an average resolution of 7.76 +/- 3.80 cM (Marshfield). In an affected-only-design (affected sib pairs), we performed nonparametric multipoint linkage analyses. Conditional analyses were applied where linkage signals were found in the baseline analyses. RESULTS: We identified two loci with nominal evidence for linkage on chromosomes 1p36.13 and 16p12.2 (D1S3669, 37.05 cM, logarithmic odds ratio [LOD] = 1.49, p = 0.004; D16S403, 43.89 cM, LOD = 1.85, p = 0.002). D16S403 crossed the empirically obtained threshold of genome-wide suggestive significance of LOD = 1.51. Positive findings in those regions have been reported by the following other linkage studies on: (1) symptomatic/clinical gall bladder disease with type 2 diabetes in Mexican Americans from the San Antonio Family Diabetes/Gallbladder Study (LOD = 3.7, D1S1597-D1S407, 29.93-33.75 cM); (2) body size-adiposity in another Mexican American population (D1S1597, LOD = 2.53, 29.93 cM); (3) lipid abnormalities (LOD = 3.1, D1S2826-D1S513, 41.92-60.01 cM); and (4) hypertension in Australian sib pairs (LOD = 3.1, D1S2834-D1S2728, 31.02-33.75 cM); as well as (5) a meta-analysis of four European type 2 diabetes-related genome scans (LOD = 1.09, D16S412, 42.81 cM). In linkage analyses conditional on evidence for linkage at D16S403 we identified a LOD increase (Delta LOD) of 1.55 (p = 0.0075) at D17S2180. Similar conditioning on D17S2180 revealed evidence for interaction with D1S3669 (Delta LOD = 1.67, p = 0.0055), D16S403 (Delta LOD = 1.48, p = 0.0091) and another locus on chromosome 1 where several genome scans have reported evidence for linkage ( approximately 200 cM, Delta LOD = 1.60, p = 0.0066). CONCLUSIONS/INTERPRETATION: Our results and the findings of other studies are consistent with the presence of a locus for a complex metabolic syndrome on chromosome 1p36.13.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Clinical science; Conditional linkage analysis; Genetics of type 2 diabetes; Genomewide scan; Linkage studies; Metabolic syndrome; Susceptibility region
Language english
Publication Year 2007
HGF-reported in Year 2007
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 50, Issue: 7, Pages: 418-1422 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503900-003
PubMed ID 17464498
DOI 10.1007/s00125-007-0658-4
WOS ID 000247210800010
Scopus ID 34249936215
Erfassungsdatum 2007-04-27
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