Human Molecular Genetics, 2003, Vol. 12, No. 15 1865-1873
DOI: 10.1093/hmg/ddg195
© 2003 Oxford University Press
A meta-analysis of four European genome screens (GIFT Consortium) shows evidence for a novel region on chromosome 17p11.2–q22 linked to type 2 diabetes
1EMI 0006, INSERM-Université d'Evry, Evry, France, 2Biocomputing Platforms Ltd Oy, Helsinki, Finland, 3Department of Endocrinology, Wallenberg Laboratory, Malmö University Hospital, SE-205 02 Malmö, Sweden, 4Wellcome Trust Centre for Human Genetics, Oxford, UK, 5Institute of Biology-CNRS 8090, Institut Pasteur, Lille, France, 6Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK, 7Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland and 8Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK
Received March 11, 2003; Revised May 7, 2003; Accepted June 2, 2003
Positional cloning is expected to identify novel susceptibility genes underlying complex traits, but replication of genome-wide linkage scan findings has proven erratic. To improve our ability to detect and prioritize chromosomal regions containing type 2 diabetes susceptibility genes, the GIFT consortium has implemented a meta-analysis of four scans conducted in European samples. These included the Botnia I and Botnia II scans, with respectively 58 and 353 pedigrees from Finland and Sweden, the Warren 2 scan performed in 573 multiplex sibships from the UK, and a scan of 143 families from France. The meta-analysis was implemented using the genome-search analysis method (GSMA), an exploratory data analysis technique which is robust across study designs. The analysis provided evidence for linkage of type 2 diabetes to six regions, with the strongest evidence on chromosome 17p11.2–q22 (P=0.0016), followed by 2p22.1–p13.2 (P=0.027), 1p13.1–q22 (P=0.028), 12q21.1–q24.12 (P=0.029), 6q21–q24.1 (P=0.033) and 16p12.3–q11.2 (P=0.033). Linkage analysis of the pooled raw genotype data generated maximum LOD scores in the same regions as identified by GSMA. Altogether, our results have indicated that GSMA is a valuable tool to identify chromosomal regions of interest and that accumulating evidence for linkage from small peaks detected across several samples may be more important than getting a high peak in a single sample. This meta-analysis has led to identification of a novel region on chromosome 17 linked to type 2 diabetes; this region has not been highlighted in any published scan to date but on the basis of these data justifies further exploration.
* To whom correspondence should be addressed. Tel: +46 40332303; Fax: +46 40337023; Email: leif.groop{at}endo.mas.lu.se
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