A locus affecting obesity in human chromosome region 10p12

Abstract

Obesity is a multigenic trait that is a major risk factor for a number of common diseases, particularly Type II (non-insulin-dependent) diabetes mellitus, cardiovascular disease and hypertension. A recent review reported a total of 44 genomic locations with possible linkage to one or more obesity-related phenotypes [1]. Because false positive findings are common in genome scans for complex traits, replication is essential before undertaking gene identification studies. Previously, linkages for obesity traits have been replicated in three regions, 2p21, 7q31, and 20q13 [1].To date one of the strongest findings of linkage was reported by French investigators, linking obesity (BMI ³ 27 kg/m 2 ) to markers in chromosome 10p12 [2]. Recently [3], these results were replicated in a cohort of German families. In our previous genome scan [4], we did not find significant linkage to this region, although we did find secondary linkages for centromeric and distal 10 q markers, corresponding to secondary peaks found in the French study for a leptin phenotype. Our genome scan had a relatively small sample size of only 92 families and we examined more extreme levels of obesity (BMI ³ 30 kg/m 2 and BMI ³ 40 kg/m 2 ) and we did not have dense marker coverage in the region of the French linkage finding.In the current analysis, we examined linkage in this region in cohorts of 170 European-American and 43 African-American families (including the 92 families from the original genome scan). AbstractAims/hypothesis. Obesity is a complex trait influenced by multiple genes. We evaluated linkage in three regions of human chromosome 10 previously linked to obesity-related phenotypes. Methods. We conducted non-parametric linkage analysis of obesity-related phenotypes in cohorts of 170 European-American and 43 African-American families having extremely obese and normal weight subjects.

Genome-wide Linkage Analysis for Severe Obesity in French Caucasians Finds Significant Susceptibility Locus on Chromosome 19q

“…We have previously reported in the French Caucasian population three regions of linkage with obesity on chro-mosomes 2, 5, and 10p, which have been confirmed in other ethnic groups (31,32). However, this first French sample set only included a small number (n ϭ 66) of sibships with both individuals possessing the severe form of obesity (BMI Ն35 kg/m 2 ), which in our view justified a specific and adequately powered genome-wide analysis focused at the more extreme end of the phenotype.…”

Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: The HyperGEN Study

“…Early reports indicated relatively consistent findings for 10p from three studies of US European American, French, and German cohorts. [19][20][21]63 Subsequently, several other reports on obesity-related phenotypes have found signals in the same or nearby chromosomal regions, but also including signals on 1q, 12 12,27 None of these studies have reported sex-specific linkage findings.…”

Loci Contributing to Adult Height and Body Mass Index in African American Families Ascertained for Type 2 Diabetes

“…Relatively high heritability estimates in the range 0.43-0.64 have also been reported for BMI (Luke et al 2001;Perola et al 2001;Wu et al 2002;Brown et al 2003;Schousboe et al 2004), although lower estimates have also been reported (e.g., Platte et al 2003). There have been numerous genomewide scans of BMI, reviewed in Chagnon et al (2003), although only five genome scans report regions of linkage for BMI in African Americans (Price et al 2001;Kotchen et al 2002;Wu et al 2002;Zhu et al 2002;Palmer et al 2004).…”