Validation of potential beef tenderness markers and interpretation of their biological functions

Human and Animal Development Regulatory Mechanisms Session 12 : Experimental epileptology and neurodegenerationabsen

Peak allelic associations within genomic regions of sarcoidosis ancestry linkage with Scadding stage IV disease.

<p>Abbreviations: f_CEU: frequency of modeled allele in HapMap Northern and Western European ancestry population; f_AFR: frequency of modeled allele in HapMap Yoruban African ancestry population; f_AFF: frequency of modeled allele in sarcoidosis-affected individuals; f_UNF: frequency of modeled allele in unaffected individuals; OR: odds ratio; 95%CI: 95% confidence interval; P: p-value; MIX: MIXSCORE test.</p>1<p>Minor allele in African Americans is bolded; modeled by generalized estimating equations adjusting for percent global West African ancestry and sex.</p>2<p>Accuracy of imputation was assessed for SNPs with p-values <10⁻⁵ in a sub-sample; agreements overall and by genotype are reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092646#pone.0092646.s004" target="_blank">Table S2</a>. Overall imputation accuracy was 96.0% (rs6547087), 99.2% (rs906233), and 99.3% (rs12919626).</p>3<p>For rs145044562, conditional on rs12919626; for rs1077963, conditional on rs145044562 and rs12919626;</p>4<p>No carriers of the A allele of rs145044562 exist within HapMap or 1000 Genomes Project European populations.</p

Heritability of sarcoidosis risk attributable to difference in local ancestry overall and by radiographic phenotypes.

<p>Note: Number of controls (n = 859) is the same across case analysis strata.</p><p>Abbreviations: N: number of cases; : proportion of additive genetic variance due the common variants (minor allele frequency ≥1%); :the proportion of the additive genetic variance due to local West African ancestry; SE: standard error of ; P: p-value from a one-degree-of-freedom likelihood ratio test of the additive genetic variance component.</p>1<p>For these analyses, the corresponding admixture locus was removed to estimate the effect on the heritability estimate.</p>2<p>These analyses were restricted to the subset of cases with a minimum of two years of follow-up.</p

Representative pictures of XAF1 and XIAP staining of sarcoidosis-affected tissues.

<p>Panels A–D depict XAF-1 staining; panels E–H depict XIAP staining. Panels A and B are bronchial mucosa; E and F are lung tissue; C and G are liver tissue; and D and H are skin tissue. In general, XAF1 staining is negative in sarcoidosis-affected areas and limited to epithelial cells at the periphery (white arrows). XIAP staining was positive, with greater intensity observed in non-caseating granulomas.</p

Genevar results suggest SNP rs6502976* is an eQTL for <i>XAF1</i>.

<p>Abbreviations: r²: linkage disequilibrium r² measure; OR: odds ratio; 95%CI: 95% confidence interval; P: p-value; Correlation: Pearson correlation coefficient.</p>1<p>Linkage disequilibrium r² measure with rs6502976 in 250 unrelated African American controls from this study; SNP rs6502976 was not genotyped in either study.</p>2<p>Minor allele in African Americans bolded; modeled by generalized estimating equations adjusting for percent global West African ancestry and sex.</p>3<p>Pearson correlation values for genotype by <i>XAF1</i> expression level (Illumina probe identifier ILMN_2370573); the direction of the correlation corresponds to an increasing numbers of the minor allele in African Americans, which is the allele that is associated with sarcoidosis risk reduction.</p>4<p>Nica et al 2011. Correlation results reported for twin 1; results were consistent for twin 2.</p>5<p>Dimas et al 2009. SNP rs9891567 was not genotyped as part of this study.</p

Altered IL-6 and IP-10 levels in SLE patients and lupus relatives.

<p>Plasma levels of IL-6 (<b>A, C</b>) and IP-10 (<b>B, D</b>) were assessed in SLE patients (case), unaffected first-degree relatives of SLE patients (FDR), and unrelated, unaffected controls with no family history of SLE (Ctl). IL-6 (<b>C</b>) and IP-10 (<b>D</b>) levels are compared by genotype of associated SNPs rs76162067 and rs79711023, respectively. Data are presented as mean <u>+</u> SEM. *<i>p<0</i>.<i>05</i>, **<i>p<0</i>.<i>01</i>, ***<i>p<0</i>.<i>001</i>, ****<i>p<0</i>.<i>0001</i> by Kruskal-Wallis test with Dunn’s multiple comparison for all groups assessed (Case/FDR/Ctl [<b>A-B</b>]; Case/FDR/Ctl carrying major (CC) or minor (TC) alleles [<b>C-D</b>]). Only comparisons found to be statistically significant were marked.</p

European-American Study Participants.

<p>European-American Study Participants.</p

Genotypic Associations between <i>IFIH1</i> and Immune Mediators.

<p>Zoom plots of associations between SNPs in <i>IFIH1</i> and box-cox transformed plasma levels of (<b>A</b>) IL-6, (<b>B</b>) TNF-α, (<b>C</b>) IFN-β, (<b>D</b>) IP-10, (<b>E</b>) anti-dsDNA, and (<b>F</b>) total number of positive lupus-associated autoantibody specificities (dsDNA, chromatin, Ro/SSA, La/SSB, Sm, SmRNP, and nRNP, as described in <i>Materials and Methods</i>), displayed as negative log transformed p-values (y-axis). Red dots indicate SNPs within Exon 13. LD map of <i>IFIH1</i> SNPs is presented (<b>G</b>).</p

IFIH1 effect on plasma levels of IL-6 and IP-10.

<p>Exon map of IFIH1 is presented (<b>A</b>) containing labeled SNPs rs76162067 and rs79711023. IL-6 (<b>B</b>) and IP-10 (<b>C</b>) levels in study participants expressing the major (CC) or minor (CT) allele of SNP rs76162067 or rs79711023, respectively, are expressed as box-cox transformed (left y-axis) and concentration (right y-axis) values. Exon order is displayed L-R for ease of interpretation, although IFIH1 is transcribed R-L from the negative strand. Data in <b>B-C</b> are presented as median ± interquartile range. *<i>p≤0</i>.<i>05</i>, **<i>p<0</i>.<i>01</i> Mann-Whitney test.</p

Genome-Wide Association Study of African and European Americans Implicates Multiple Shared and Ethnic Specific Loci in Sarcoidosis Susceptibility

<div><p>Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, <em>NOTCH4</em>, that reached genome-wide significance in the combined AA samples (rs715299, <em>P</em>_AA-meta = 6.51×10⁻¹⁰) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within <em>HLA-DRA, HLA-DRB5, HLA-DRB1</em>, <em>BTNL2,</em> and <em>ANXA11</em> in both our AA and EA datasets. We also confirmed significant associations to the previously reported <em>HLA-C</em> and <em>HLA-B</em> regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.</p> </div