Additional file 8 of On the impact of relatedness on SNP association analysis

Perl script for converting HapMap genotype data. This Perl script requires the sample list of Additional file 6, the SNP list of Additional file 7 and HapMap raw data. The HapMap project website is not available anymore, however, genotype data can still be retrieved from ftp://ftp.ncbi.nlm.nih.gov/hapmap/genotypes/2010-08_phaseII+III/ . The converted genotypes are saved in a CSV file. Folder and file locations must be adapted before running the script. Running the script on an Intel Xeon X5560 CPU (2.80 GHz) required 800 MB RAM and took about 5 minutes. (PL 2 kb

Acylcarnitines serum concentration in individuals with normal glucose tolerance (NGT), isolated impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT) and type 2 diabetes (T2D).

<p>± standard deviation and ranges. P-values are corrected for age, gender and BMI. Tukey-HSD post-hoc test was performed only when the adjusted ANOVA showed significant differences. Data present means </p

Association between acylcarnitines and body fat or waist to hip ratio.

<p> Associations were assessed in a linear regression model adjusted for age and gender. P-values <0.05 were considered as statistically significant and marked in bold italic.</p

Serum concentration for C14:1-carnitine (A) and C3DC+C4OH-carnitine (B) in the different groups.

<p>Shown are means + SEM for NGT (normal glucose tolerance), IFG (impaired fasting glycaemia), IGT (impaired glucose tolerance) and T2D (type 2 diabetes); * p<0.05 vs. T2D, # p<0.01 vs. IGT</p

Three allelic association tests on <i>FTO</i> with BMI variation in the Sorbs data set.

<p>Different association tests are shown: top) standard association; below left) association using paternal alleles; below right) association using maternal alleles with BMI in the Sorbs adjusted for age, sex and T2D. Positions of SNPs are based on Genome Reference Consortium GRCh37. Intron 1 and 3 of <i>FTO</i> are highlighted by rectangles. Regional plots were generated by using LocusZoom version 1.1 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119206#pone.0119206.ref040" target="_blank">40</a>].</p

Linkage disequilibrium (LD) for all 27 SNPs in introns 1 to 3 of <i>FTO</i> in the Sorbs.

<p>Linkage disequilibrium (LD) for all 27 SNPs in introns 1 to 3 of <i>FTO</i> in the Sorbs.</p

Identification of Adipokine Clusters Related to Parameters of Fat Mass, Insulin Sensitivity and Inflammation

<div><p>In obesity, elevated fat mass and ectopic fat accumulation are associated with changes in adipokine secretion, which may link obesity to inflammation and the development of insulin resistance. However, relationships among individual adipokines and between adipokines and parameters of obesity, glucose metabolism or inflammation are largely unknown. Serum concentrations of 20 adipokines were measured in 141 Caucasian obese men (n = 67) and women (n = 74) with a wide range of body weight, glycemia and insulin sensitivity. Unbiased, distance-based hierarchical cluster analyses were performed to recognize patterns among adipokines and their relationship with parameters of obesity, glucose metabolism, insulin sensitivity and inflammation. We identified two major adipokine clusters related to either (1) body fat mass and inflammation (leptin, ANGPTL3, DLL1, chemerin, Nampt, resistin) or insulin sensitivity/hyperglycemia, and lipid metabolism (vaspin, clusterin, glypican 4, progranulin, ANGPTL6, GPX3, RBP4, DLK1, SFRP5, BMP7, adiponectin, CTRP3 and 5, omentin). In addition, we found distinct adipokine clusters in subgroups of patients with or without type 2 diabetes (T2D). Logistic regression analyses revealed ANGPTL6, DLK1, Nampt and progranulin as strongest adipokine correlates of T2D in obese individuals. The panel of 20 adipokines predicted T2D compared to a combination of HbA1c, HOMA-IR and fasting plasma glucose with lower sensitivity (78% versus 91%) and specificity (76% versus 94%). Therefore, adipokine patterns may currently not be clinically useful for the diagnosis of metabolic diseases. Whether adipokine patterns are relevant for the predictive assessment of intervention outcomes needs to be further investigated.</p></div

Multivariate-adjusted odds ratios of adipokines as predictors of type 2 diabetes in obese individuals (n = 141).

<p>Logistic regression analysis: regression coefficients (B), standard errors (SE), odds ratios (OR), p-values and Nagelkerke r² for prediction models of T2D in 141 obese individuals. Model 1 includes all 20 adipokines, model 2 shows the parameters with the strongest predictive value for T2D as result of a backwards stepwise method. Abbreviations: BMI, body mass index; ANGPTL 3, angiopoietin-like protein 3; ANGPTL 6, angiopoietin-like protein 6; BMP7, bone morphogenetic protein 7; CTRP3, complement C1q tumor necrosis factor-related protein 3; CTRP5, complement C1q tumor necrosis factor-related protein 5; DLL1, delta-like protein 1; DLK1, preadipocyte factor 1; GPX3, glutathione peroxidase 3; Nampt, nicotinamide phosphoribosyltransferase (visfatin); RBP4, retinol binding protein 4; SFRP5, secreted frizzled-related protein-5.</p

Hierarchical clustering of 20 serum adipokine concentrations in obese patients (n = 141).

<p>We provide approximately unbiased (AU, numbers in red) p-values and bootstrap probability (numbers in green) values as measures of certainty for clusters. Values are based on 10,000 bootstrapping replicates. AU≥90% was considered as strong evidence for the cluster and is marked by red rectangles (only largest possible clusters are marked). Abbreviations: CRP, high sensitive C-reactive protein; ANGPTL 3, angiopoietin-like protein 3; ANGPTL 6, angiopoietin-like protein 6; BMP7, bone morphogenetic protein 7; CTRP3, complement C1q tumor necrosis factor-related protein 3; CTRP5, complement C1q tumor necrosis factor-related protein 5; LPS, Lipopolysacharid (Endotoxin); GPX3, glutathione peroxidase 3; DLL1, delta-like protein 1; DLK1, preadipocyte factor 1; NAMPT, nicotinamide phosphoribosyltransferase (visfatin); RBP4, retinol binding protein 4; SFRP5, secreted frizzled-related protein-5; TG, triglycerides.</p

Association of <i>vaspin</i> genetic variants with eating behaviour phenotypes (N = 548).

<p>Data represent subjects without type 2 diabetes. <i>P</i>-values were calculated by linear regression analysis, after adjusting for age, gender and BMI in the additive mode of inheritance and are presented without correction for multiple testing. <i>P</i>-values <0.05 are in bold. ß (regression coefficient) is standardized to the minor allele. SNP = single nucleotide polymorphism; BMI = body mass index.</p