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Impact of obesity-related genes in Spanish population.

Martínez-García F, Mansego ML, Rojo-Martínez G, De Marco-Solar G, Morcillo S, Soriguer F, Redón J, Pineda Alonso M, Martín-Escudero JC, Cooper RS, Chaves FJ - BMC Genet. (2013)

Bottom Line: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001).None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis.A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hypertension Clinic, Hospital Clínico Universitario and INCLIVA, University of Valencia, Valencia 46010, Spain. josep.redon@uv.es.

ABSTRACT

Background: The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis.

Results: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%).

Conclusion: The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

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Related in: MedlinePlus

Combined impact of risk alleles on average BMI in the pooled analysis. For each individual, the number of risk alleles (0,1,2) per SNP was weighted for their effect sizes and re-scaled by dividing by the average of the all the effect sizes. The weighted risk alleles for the selected SNPs were summed for each individual, and the overall individual sum was rounded to the nearest integer to represent the individual’s risk allele score. Along the x axis, individuals in each risk allele category are shown (grouped ≤2 and ≥6 at the extremes), and the mean BMI (± s.e.m.) is plotted (y axis on right), with the line representing the regression of the mean BMI values across the risk allele scores. The histogram (y axis on left) represents the number of individuals for each risk-score category.
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Figure 1: Combined impact of risk alleles on average BMI in the pooled analysis. For each individual, the number of risk alleles (0,1,2) per SNP was weighted for their effect sizes and re-scaled by dividing by the average of the all the effect sizes. The weighted risk alleles for the selected SNPs were summed for each individual, and the overall individual sum was rounded to the nearest integer to represent the individual’s risk allele score. Along the x axis, individuals in each risk allele category are shown (grouped ≤2 and ≥6 at the extremes), and the mean BMI (± s.e.m.) is plotted (y axis on right), with the line representing the regression of the mean BMI values across the risk allele scores. The histogram (y axis on left) represents the number of individuals for each risk-score category.

Mentions: The score constructed with the sum of the weighed risk alleles was positively correlated with BMI in Pizarra and in the pooled sample (r = 0.15 in Pizarra, p-value < 0.001; r = 0.082 in the pooled sample, p-value < 0.001). From the first to the fifth quintile of the score, the BMI increases 2 Kg/m2 in Pizarra, 0.45 Kg/m2 in Hortega and 0.93 Kg/m2 in the pooled analysis. The BMI values for each quintile of the score as well as the regression line between BMI and the risk score is shown in Figure 1. However, the variance of BMI associated to individual SNPs or to the score was very low (less than 1%). The predictive value of the score for obesity was poor [area under the curve (AUC) 0.515 and 0.594 in Hortega and Pizarra respectively] (Additional file 5: Figure S3).


Impact of obesity-related genes in Spanish population.

Martínez-García F, Mansego ML, Rojo-Martínez G, De Marco-Solar G, Morcillo S, Soriguer F, Redón J, Pineda Alonso M, Martín-Escudero JC, Cooper RS, Chaves FJ - BMC Genet. (2013)

Combined impact of risk alleles on average BMI in the pooled analysis. For each individual, the number of risk alleles (0,1,2) per SNP was weighted for their effect sizes and re-scaled by dividing by the average of the all the effect sizes. The weighted risk alleles for the selected SNPs were summed for each individual, and the overall individual sum was rounded to the nearest integer to represent the individual’s risk allele score. Along the x axis, individuals in each risk allele category are shown (grouped ≤2 and ≥6 at the extremes), and the mean BMI (± s.e.m.) is plotted (y axis on right), with the line representing the regression of the mean BMI values across the risk allele scores. The histogram (y axis on left) represents the number of individuals for each risk-score category.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222487&req=5

Figure 1: Combined impact of risk alleles on average BMI in the pooled analysis. For each individual, the number of risk alleles (0,1,2) per SNP was weighted for their effect sizes and re-scaled by dividing by the average of the all the effect sizes. The weighted risk alleles for the selected SNPs were summed for each individual, and the overall individual sum was rounded to the nearest integer to represent the individual’s risk allele score. Along the x axis, individuals in each risk allele category are shown (grouped ≤2 and ≥6 at the extremes), and the mean BMI (± s.e.m.) is plotted (y axis on right), with the line representing the regression of the mean BMI values across the risk allele scores. The histogram (y axis on left) represents the number of individuals for each risk-score category.
Mentions: The score constructed with the sum of the weighed risk alleles was positively correlated with BMI in Pizarra and in the pooled sample (r = 0.15 in Pizarra, p-value < 0.001; r = 0.082 in the pooled sample, p-value < 0.001). From the first to the fifth quintile of the score, the BMI increases 2 Kg/m2 in Pizarra, 0.45 Kg/m2 in Hortega and 0.93 Kg/m2 in the pooled analysis. The BMI values for each quintile of the score as well as the regression line between BMI and the risk score is shown in Figure 1. However, the variance of BMI associated to individual SNPs or to the score was very low (less than 1%). The predictive value of the score for obesity was poor [area under the curve (AUC) 0.515 and 0.594 in Hortega and Pizarra respectively] (Additional file 5: Figure S3).

Bottom Line: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001).None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis.A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hypertension Clinic, Hospital Clínico Universitario and INCLIVA, University of Valencia, Valencia 46010, Spain. josep.redon@uv.es.

ABSTRACT

Background: The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis.

Results: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%).

Conclusion: The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

Show MeSH
Related in: MedlinePlus