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Dear Sir, In 1994 a collaboration was initiated between the Diabetes Units in Sardinia and the Karolinska Institute in Stockholm within the framework of "The Sardinian Diabetes Genetics Study Group (SDGSG)". The aim is to identify and characterise Sardinian [1] non-insulin-dependent diabetes mellitus (NIDDM) families to study the genetics of NIDDM using both linkage and association approaches. The following minimum criteria were used to select NIDDM families from all parts of Sardinia: Sardinian ancestry for more than two generations; at least two siblings affected with NIDDM; onset of NIDDM in the probands was before 55 years; patients requiring insulin treatment within 3 years of diagnosis or with age at onset less than 30 years were excluded; if available, siblings of age above 65 years without NIDDM were included; and families with parents or offspring with insulin-dependent diabetes were excluded. All individuals were characterised for age of onset, body mass index, lipids, HbAlc, blood pressure, diabetic complications and pharmacological treatment. According to these criteria, the number of NIDDM individuals available was 431 who belonged to 173 families, making a total of 387 affected sib-pairs. Genomic DNA extracted from lymphocytes was used for analysis of linkage between NIDDM and markers spanning the whole genome. Recently Hanis et al. localised a susceptibility locus for NIDDM on chromosome 2 (NIDDM1) by a genome-wide analysis of 440 Mexican-American sib-pairs affected with NIDDM. The linkage was not confirmed in two control populations (non-Hispanic white and Japanese affected sib-pairs) [2]. This stimulated a comment on the effect of multiple affected large sibships and the required p-value for declaring significant linkage [3]. In the NIDDM gene search, it is very important to replicate the findings in other populations to prove its importance in this heterogeneous disease. Recently, a study showed that NIDDM1 is not a major diabetogenic locus in a French Caucasian population [4]. Since we have completed the analysis on chromosome 2, we investigated whether it was possible to replicate the Hanis observation in sib-pairs from Sardinia. We used 25 highly polymorphic microsatellite markers [5] spanning chromosome 2 with an average spacing of

Preliminary data on a genome search in NIDDM siblings: the NIDDM 1 locus on chromosome 2 is not linked to NIDDM in the Sardinian population