Genome-Wide Linkage Analysis Assessing Parent-of-Origin Effects in the Inheritance of Type 2 Diabetes and BMI in Pima Indians

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Abstract
We examined the hypothesis that imprinted genes may affect the propensity to type 2 diabetes and obesity in Pima Indians. Multipoint variance component methods were used to assess linkage of BMI (kg/m2) and age-adjusted diabetes to loci derived from either father (LODFA) or mother (LODMO) in a genome-wide scan. Tentative evidence of loci where imprinted genes might be acting was found for diabetes with maternally derived alleles on chromosomes 5 (LODMO = 1.5) and 14 (LODMO = 1.6). Evidence of linkage of BMI to maternally derived alleles was found on chromosome 5 (LODMO = 1.7) and to paternally derived alleles on chromosome 10p (LODFA = 1.7). Additional analyses of sibling pairs who were affected by diabetes and younger than 25 years of age showed an increase of sharing of maternally derived alleles on chromosome 6 (LODMO = 3.0). We also examined sites of a priori interest where action of imprinted genes has been proposed in diabetes or obesity. We found no evidence of parent-specific linkage (of either diabetes or BMI) on chromosome 11p, a region that contains several imprinted genes, but observed weak evidence of linkage of diabetes to paternally derived alleles (LODFA = 0.9) in the region of chromosome 6q, believed to contain an exclusively paternally expressed gene or genes that cause transient neonatal diabetes mellitus. In conclusion, we determined regions of interest on chromosomes 5, 6, and 10 where imprinted genes might be affecting the risk of type 2 diabetes or obesity in Pima Indians.