A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population

A total of 896 individuals of Ashkenazi Jewish descent were ascertained in Israel from 267 multiplex families, including 472 sib-pairs affected with t ype 2 diabetes. A genome-wide scan with average marker spacing of 9.5 cM re vealed five regions on four chromosomes (4q, 8q, 14q, and 20q) that exhibit ed nominal evidence for linkage (P < 0.05). The highest observed nonparamet ric linkage Z score was 2.41 (equivalent to a logarithm of odds score of 1. 26) at marker D4S1501. A maximal signal, with a Z score of 2.05, was observ ed on chromosome 20 near marker D20S195, and another on 20p near marker D20 S103 (Z 1.80). A single marker on chromosome 8 (D8S593) and two adjacent ma rkers on chromosome 14 (D14S749 and D14S605) also attained evidence of link age. To explore the hypothesis that the signals on chromosomes 4 and 20 are differentially attributable to variation in BMI or age of onset, an ordere d subset analysis was conducted. This analysis revealed that only when the families were ranked by BMI tin increasing order) did a subset attain nomin al significance, and only for chromosome 4. The findings reported here lend credence to the hypothesis, now supported by four studies of Caucasian pop ulations and most recently by a combined analysis of 1,852 pedigrees, that a type 2 diabetes susceptibility locus resides on chromosome 20q. This popu lation, because of its unique genetic attributes, may facilitate identifica tion of this and other genes contributing to type 2 diabetes.