Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A young onset of type 2 diabetes is likely to result, in part, from greater genetic susceptibility. Young-onset families may therefore represent a group in which genes are more easily detectable by linkage. To test this hypothesis, we conducted age at diagnosis (AAD) stratified linkage analyses in the Diabetes UK Warren 2 sibpairs. In the previously published unstratified analysis, evidence for linkage (logarithm of odds [LOD] >1.18) was found at seven loci. The LOD scores at these seven loci were higher in the 245 families with AAD <55 years (L55) compared with the 328 families with AAD >55 years (G55). Five of these seven loci (1q24-25, 5q13, 8p21-22, 8q24.2, and 10q23.2) had LOD scores >1.18 in the L55 subset but only one (8p21-22) did in the G55 subset. Two additional loci (8q21.13 and 21q22.2) showed evidence for linkage in the L55 subset alone. Another locus (22q11) showed evidence for linkage in a subset of families with AAD <45 years. Using a locus-counting approach, the L55 subset had significantly more loci (P approximately 0.01) than expected under the null hypothesis of no linkage across the LOD score range 0.59-3.0. In contrast, the G55 subset contained no more susceptibility loci than that expected by chance. In conclusion, young-onset families provide both disproportionate evidence for linkage to known loci and evidence for additional novel loci. Our data confirm our hypothesis that families segregating young-onset type 2 diabetes represent a more powerful resource for defining susceptibility genes by linkage.

Original publication




Journal article



Publication Date





1857 - 1863


Age of Onset, Aged, Chromosome Mapping, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 8, Diabetes Mellitus, Type 2, Family, Female, Genome, Human, Humans, Lod Score, Male, Middle Aged, United Kingdom