Limits...
Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study.

Franceschini N, Almasy L, MacCluer JW, Göring HH, Cole SA, Diego VP, Laston S, Howard BV, Lee ET, Best LG, Fabsitz RR, North KE - BMC Med. Genet. (2008)

Bottom Line: Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02).In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7).These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. noraf@unc.edu

ABSTRACT

Background: Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS) participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4).

Methods: SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs) influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses.

Results: Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02). In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7). This chromosome region harbors the adiponectin receptor 1 gene, which has been previously associated with obesity.

Conclusion: These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.

Show MeSH

Related in: MedlinePlus

Multipoint LOD Scores on Chromosome 1 for Weight by Diabetes Status. Adjusted for age, age2, sex, age-by-sex interaction within centers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2572048&req=5

Figure 2: Multipoint LOD Scores on Chromosome 1 for Weight by Diabetes Status. Adjusted for age, age2, sex, age-by-sex interaction within centers.

Mentions: Analysis accounting for the genotype-by-diabetes interaction identified a QTL for weight on chromosome 1 at 242 cM (marker D1S249, LOD = 3.7) (Figure 1). For comparison, the diabetes-specific signal at 1q32 for other obesity-related traits is also shown in Figure 1. Stratified analyses by diabetes showed that the chromosome 1 signal was more prominent in diabetic subjects (LOD = 2.7) (Figure 2). The 1-LOD support interval was between D1S238 and D1S425 covering the regions 1q31.1-q32.2, and approximately 23.8 MB. Additional QTLs identified in our linkage analysis of obesity traits accounting for diabetes status are reported in the Additional file 1.


Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study.

Franceschini N, Almasy L, MacCluer JW, Göring HH, Cole SA, Diego VP, Laston S, Howard BV, Lee ET, Best LG, Fabsitz RR, North KE - BMC Med. Genet. (2008)

Multipoint LOD Scores on Chromosome 1 for Weight by Diabetes Status. Adjusted for age, age2, sex, age-by-sex interaction within centers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572048&req=5

Figure 2: Multipoint LOD Scores on Chromosome 1 for Weight by Diabetes Status. Adjusted for age, age2, sex, age-by-sex interaction within centers.
Mentions: Analysis accounting for the genotype-by-diabetes interaction identified a QTL for weight on chromosome 1 at 242 cM (marker D1S249, LOD = 3.7) (Figure 1). For comparison, the diabetes-specific signal at 1q32 for other obesity-related traits is also shown in Figure 1. Stratified analyses by diabetes showed that the chromosome 1 signal was more prominent in diabetic subjects (LOD = 2.7) (Figure 2). The 1-LOD support interval was between D1S238 and D1S425 covering the regions 1q31.1-q32.2, and approximately 23.8 MB. Additional QTLs identified in our linkage analysis of obesity traits accounting for diabetes status are reported in the Additional file 1.

Bottom Line: Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02).In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7).These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. noraf@unc.edu

ABSTRACT

Background: Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS) participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4).

Methods: SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs) influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses.

Results: Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02). In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7). This chromosome region harbors the adiponectin receptor 1 gene, which has been previously associated with obesity.

Conclusion: These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.

Show MeSH
Related in: MedlinePlus