Body Mass Index Quantitative Trait Locus 11

For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641.

Mapping

Obesity (see 601665) is a multifactorial trait with evidence of a genetic component. Obesity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m(2) or more. Ohman et al. (2000) reported results from a 3-stage genomewide scan of obesity in 188 affected subjects (BMI, 32 kg/m(2) or more) from 87 Finnish families. Initially, 374 markers with an average density of 10 cM were genotyped. The strongest evidence for linkage to obesity was detected on chromosome Xq24, with the marker DXS6804 providing a maximum likelihood score (MLS) of 3.14 in a model-free 2-point sib pair analysis. Fine mapping in an extended sample set of 367 affected subjects from 166 families yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, that encoding the serotonin 2C receptor (312861), variants of which have been shown to predispose to obesity and type II diabetes (NIDDM; 125853) in mice.

In 218 obese Finnish sib pairs, Suviolahti et al. (2003) genotyped microsatellite markers and SNPs for 11 positional and functional candidate genes in the 15-Mb region on Xq24 previously identified by Ohman et al. (2000) and narrowed the critical interval to 4 Mb between DXS8088 and DXS8067. Evidence of linkage emerged mainly from the obese male sib pairs, suggesting a gender-specific effect for the underlying gene. Suviolahti et al. (2003) detected significant associations between susceptibility to obesity and SNPs in exon 14 (22510C-G) and in intron 12 (20649C-T) of the SLC6A14 gene (300444) (p = 0.0002 and 0.07, respectively). The 22510C-G SNP, also designated exon 14 +326, is located in the 3-prime untranslated region and was the SNP that showed the strongest association with obesity in this study. An independent replication sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and nonobese individuals (p = 0.003). The association was predominantly in females and extended to SNP haplotypes of the SLC6A14 gene. Suviolahti et al. (2003) noted that gender-specific differences in the prevalence of severe obesity are well established, with females more often affected than males in Finland, and stated that SLC6A14 is an interesting candidate gene for obesity because it encodes an amino acid transporter which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control.

Durand et al. (2004) genotyped 1,267 obese French adults and 649 lean controls for the SLC6A14 SNPs 22510C-G (rs2011162) and 20649C-T (rs2071877) and confirmed the association with obesity in the French population (OR, 1.23 and p = 0.013, and OR, 1.36 and p = 0.0001, respectively).