Percent body fat distributions for the 36 RNAi knock down Drosophila gene crosses, testing significantly different from corresponding Wild Type control, by Dunnett’s multiple comparisons test.

<p>Percent body fat distributions for the 36 RNAi knock down Drosophila gene crosses, testing significantly different from corresponding Wild Type control, by Dunnett’s multiple comparisons test.</p

Percent body fat distributions for the 36 RNAi knock down Drosophila gene crosses, testing significantly different from corresponding Wild Type control, by Dunnett’s multiple comparisons test.

<p>Percent body fat distributions for the 36 RNAi knock down Drosophila gene crosses, testing significantly different from corresponding Wild Type control, by Dunnett’s multiple comparisons test.</p

Results of the functional drosophila screen for all genes nearby (± 250 kb) the 78 BMI-associated GWAS loci from speliotes et al. 2010[30] and locke et al. 2015[31].

<p>Results of the functional drosophila screen for all genes nearby (± 250 kb) the 78 BMI-associated GWAS loci from speliotes et al. 2010[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007222#pgen.1007222.ref030" target="_blank">30</a>] and locke et al. 2015[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007222#pgen.1007222.ref031" target="_blank">31</a>].</p

Summary of Drosophila functional scan for the 61 BMI GWAS loci that could be tested in the fly.

<p>Number of GWAS BMI loci for which nearby genes were validated in RNAi KDs in Drosophila. <b>(a)</b> Distribution of Number of Significant Fly KD Genes per BMI Locus Region. Significance determined by Dunnett’s Multiple Comparisons Test. <b>(b)</b> Number of Significant Fly KD Genes per BMI Locus by Proximity to SNP. Significance determined by Dunnett’s Multiple Comparisons Test. CNBT = Could Not Be Tested in Fly (either No Fly Ortholog or KD lethal).</p

Experimental design of the Drosophila BMI loci functional screen.

<p>WT = Corresponding RNAi Wild Type (as detailed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007222#pgen.1007222.g003" target="_blank">Fig 3</a>).</p

Association of SNPs from a Recently Published GWAS of Body Fat Distribution^* (Heid IM et al, NG, 2010) [32].

<p>All data modeled relative to the previously-published trait-increasing allele; the z-statistic indicates the effect direction relative to the coded allele.</p>*<p>Measured by WHR-adjusted-for-BMI.</p

Association of validated SNPs for BMI (from Speliotes et al, Nature Genetics 2010) [39].

<p>All CT traits presented with the same coded allele, and all are modeled relative to the previously-published BMI trait-increasing allele. Z-statistic indicates direction relative to the coded allele.</p

Results of rs1659258 in the VATGen meta-analysis; results modeled per copy of the trait-increasing A allele and for independent validation in the GIANT Consortium (non-overlapping studies).^*

*<p>GIANT sample sizes for women and men are as follows: BMI (58208, 49092); WC (39471, 31406).</p

Study Sample Characteristics, VATGen Consortium.

<p>Data shown as mean (standard deviation) unless otherwise indicated.</p>*<p>cm3 for the Framingham Heart Study; all other studies are measured in cm2.</p

Novel loci associated with eGFRcrea.

<p>SNPs are listed in the stratum where the smallest <i>P</i> value in the discovery analysis was observed. Sample size/number of studies in the discovery phase: 74,354/26 (overall, direction test), 66,931/24 (No Diabetes), 46,435/23 (age ≤65 years); replication phase: 56,246/19 (overall, direction test), 41,218/17 (No Diabetes), 28,631/16 (age ≤65 years); combined analysis: 130,600/45 (overall, direction test), 108,149/41 (No Diabetes), 75,066/39 (age ≤65 years).</p><p>Chr.: chromosome; bp: base-pairs; Ref./Non-Ref. All.: reference/non-reference alleles; RAF: reference allele frequency; SE: standard error.</p>‡<p>Genes nearby were based on RefSeq genes (build 36). The gene closest to the SNP is listed first and is in boldface if the SNP is located within the gene.</p>§<p>Effects on log(eGFRcrea); post GWAS meta-analysis genomic control correction applied to <i>P</i> values and SEs.</p>*<p>While being uncovered in the younger samples, this locus showed consistent results in the non-diabetic group (combined-analysis <i>P</i> value 5.7×10⁻¹⁶) and in the overall population (<i>P</i> value 9.5×10⁻²²) - see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002584#pgen.1002584.s028" target="_blank">Tables S16</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002584#pgen.1002584.s022" target="_blank">S10</a> for additional details.</p>**<p>The direction test was performed in the overall dataset; the genomic control corrected <i>P</i> value from the direction test for the SNP rs2928148 was 4.0×10⁻⁷. In the combined analysis, the largest effect size (0.0054 on log eGFR in ml/min/1.73 m²) and the smallest <i>P</i> value (3.7×10⁻⁸) were observed in the non-diabetic group.</p>†<p>All results were confirmed by random-effect meta-analysis.</p