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

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Title:	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
Creators Name:	Hoffmann, K., Mattheisen, M., Dahm, S., Nuernberg, P., Roe, C., Johnson, J., Cox, N.J., Wichmann, H.E., Wienker, T.F., Schulze, J., Schwarz, P.E. and Lindner, T.H.
Abstract:	Aims/hypothesis: 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 (∼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.
Keywords:	Clinical Science, Conditional Linkage Analysis, Genetics of Type 2 Diabetes, Genomewide Scan, Linkage Studies, Metabolic Syndrome, Susceptibility Region
Source:	Diabetologia
ISSN:	0012-186X
Publisher:	Springer
Volume:	50
Number:	7
Page Range:	1418-1422
Date:	July 2007
Official Publication:	https://doi.org/10.1007/s00125-007-0658-4
PubMed:	View item in PubMed

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