Genetic association of <i>FTO/IRX</i> region with obesity and overweight in the Polish population

<div><p>Background/Objectives</p><p>Genome-wide association studies (GWAS) have identified many <i>loci</i> associated with body mass index (BMI) in many different populations. Variants in the <i>FTO locus</i> are reported to be one of the strongest genetic predictors of obesity. Recent publications pointed also to a topologically associated domain (TAD) which is identified as a novel region affecting BMI. The TAD area encompasses the IRXB cluster (<i>IRX3</i>, <i>IRX5</i>, <i>IRX6</i>), <i>FTO</i> and <i>RPGRIP1L</i> genes.</p><p>Subjects/Methods</p><p>In this study, we investigated the relationship between variation of the <i>FTO</i> and <i>IRX</i> genes and obesity in Poles. We presented a case—control association analysis (normal versus overweight and/or obesity group) of Polish adult individuals (N = 5418). We determined whether or not the chromosomal region 16:53 500 000–55 500 000 contains polymorphic variants which are correlated with BMI in Polish population, including sex and age stratified analysis.</p><p>Results</p><p>The obtained results showed that the problem of weight-height abnormalities differently affects populations of Polish women and men (χ² = 187.1; p<0.0001). From 353 SNPs enrolled to this study, 86 were statistically significant (highest χ² = 15.72; p = 7.35E-05 observed for rs1558902). Linkage disequilibrium (LD) analysis revealed 61 blocks in the tested region of chromosome 16, with 24 SNPs located within the same block (block 8) of approximately 40 kb, in almost complete LD (|D’|>0.98, r²>0.80). We confirmed presence of the genetic susceptibility <i>loci</i> located in intron 1 of the <i>FTO</i> gene, which were correlated with BMI in our study group. For the first time, our analyses revealed strong association of <i>FTO</i> intronic variants (block 8) with overweight in group of men only. We have also identified association of the <i>IRX</i> region with overweight and/or obesity in Polish individuals.</p><p>Conclusion</p><p>Our study demonstrated how tested SNPs make differential contributions to obesity and overweight risk. We revealed sex dependent differences in the distribution of tested <i>loci</i> which are associated with BMI in the population of Poles.</p></div

Numerical modelling of moisture transfers with hysteresis in cementitious materials: Verification and investigation of the effects of repeated wetting–drying boundary conditions

International audienceIn natural environment, the cover layer of reinforced concrete structures is affected by periodic variations of external relative humidity (RH). However, most moisture transport models in the literature only focus on drying of materials. In this study, a method coupling a moisture transport model with any kind of hysteresis modelling is presented. Two hysteresis models (conceptual and empirical) have been implemented and compared. The scope of the study is limited to cyclic variations of RH with no direct contact with liquid water during the wetting steps. Experimental data verifications show that the conceptual approach yields better results than the empirical one. Comparisons of non-hysteresis and hysteresis modellings have been carried out for different cycle durations, RH amplitudes and initial moisture states. All comparisons and investigations enhance the necessity of considering hysteresis to quantify moisture transport under repeated drying-wetting boundary conditions

Distribution of calculated p values in linear regression analysis.

<p>P values are expressed as negative logarithm of the p values obtained in linear regression analysis with age and sex as a covariates. The <i>y</i> axis shows the −log₁₀ p values of 262 SNPs, and the <i>x</i> axis shows their rs numbers. Horizontal blue, green and red lines represent the thresholds of p = 0.05 for significance without multiple correction, p = 8.2E-04 for LD block significance and p = 1.9E -04 for Bonferroni correction, respectively.</p

Distribution of estimated p values of the Chi square test in obesity phenotype stratified by age and sex.

<p>P values were calculated in the test of independence between the obesity phenotype and MAFs at tested SNPs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180295#pone.0180295.s008" target="_blank">S4 Table</a>). The <i>y</i> axis shows the −log₁₀ p values of 262 SNPs obtained in obesity versus normal weight association analysis, and the <i>x</i> axis shows their rs numbers. Horizontal black and green lines represent the thresholds of p = 0.05 for significance without multiple correction and p = 8.2E-04 for LD block significance, respectively. Red and blue columns represents females and males group, respectively.</p

Linkage disequilibrium analysis of 262 SNPs from chromosomal region 16:53 500 000–55 500 000.

<p>Pairwise linkage exhibited as LD coefficients (|D’|) between each pair of SNPs. Minor allele frequencies of all SNPs used in this analysis are ≥10%. Bolded triangles show haplotype blocks. Data were generated with Haploview version 4.2.</p

Distribution of estimated p values of the Chi square test in overweight phenotype stratified by age and sex.

<p>P values were calculated in the test of independence between the overweight phenotype and MAFs at tested SNPs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180295#pone.0180295.s009" target="_blank">S5 Table</a>). The <i>y</i> axis shows the −log₁₀ p values of 262 SNPs obtained in overweight versus normal weight association analysis, and the <i>x</i> axis shows their rs numbers. Horizontal black and green lines represent the thresholds of p = 0.05 for significance without multiple correction and p = 8.2E-04 for LD block significance, respectively. Red and blue columns represents females and males group, respectively.</p

Geographic residence place of recruited participants included in study group.

<p>Geographic residence place of recruited participants included in study group.</p

Pairwise differences in frequency of c.1528G>C (p.Glu510Gln) variant shown as p-values of chi-square test for alleles (with Yates correction if any subgroup was lower than 10) between populations from several countries based on literature and population of Pomeranian province including/excluding Kashubians, Kashubian population and overall population of Poland excluding Pomeranian population.

<p>Significant differences (p<0.05) were shaded.</p

Pyrosequencing results indicating presence of c.1528G>C variant.

<p>Pyrosequencing results indicating presence of c.1528G>C variant.</p

Prediction of SNP substitution on pathogenicity, analysis performed <i>in silico</i> [32].

<p>Variants predicted by different tools as deleterious were shaded.</p