Distribution by Anatomical Site and Pathological Diagnosis of Final Sample (n = 17).

<p>Distribution by Anatomical Site and Pathological Diagnosis of Final Sample (n = 17).</p

Outcomes of Molecular Analysis.

<p>Outcomes of Molecular Analysis.</p

General Characteristics of Samples Tested for HBV DNA (n = 17).

<p>General Characteristics of Samples Tested for HBV DNA (n = 17).</p

Common and rare exonic <i>MUC5B</i> variants associated with type 2 diabetes in Han Chinese

<div><p>Genome-wide association studies have identified over one hundred common genetic risk variants associated with type 2 diabetes (T2D). However, most of the heritability of T2D has not been accounted for. In this study, we investigated the contribution of rare and common variants to T2D susceptibility by analyzing exome array data in 1,908 Han Chinese genotyped with Affymetrix Axiom® Exome Genotyping Arrays. Based on the joint common and rare variants analysis of 57,704 autosomal SNPs within 12,244 genes using Sequence Kernel Association Tests (SKAT), we identified significant associations between T2D and 25 variants (9 rare and 16 common) in <i>MUC5B</i>, <i>p</i>-value 1.01×10⁻¹⁴. This finding was replicated (p = 0.0463) in an independent sample that included 10,401 unrelated individuals. Sixty-six of 1,553 possible haplotypes based on 25 SNPs within <i>MUC5B</i> showed significant association with T2D (Bonferroni corrected p values < 3.2×10⁻⁵). The expression level of <i>MUC5B</i> is significantly higher in pancreatic tissues of persons with T2D compared to those without T2D (p-value = 5×10⁻⁵). Our findings suggest that dysregulated MUC5B expression may be involved in the pathogenesis of T2D. As a strong candidate gene for T2D, <i>MUC5B</i> may play an important role in the mechanisms underlying T2D etiology and its complications.</p></div

Allele Counts by type 2 diabetes status for variants in the <i>MUC5B and ABCC12 genes</i>.

<p>Allele Counts by type 2 diabetes status for variants in the <i>MUC5B and ABCC12 genes</i>.</p

<i>MUC5B</i> differential expression in pancreatic islets from T2D and non-T2D organ donors.

<p>Displayed on the y axis are the mean and standard deviation values of log₂ transformation of expression data.</p

Top results for the joint association analyses of common and rare exome variants with T2D in Han Chinese individuals.

<p>Top results for the joint association analyses of common and rare exome variants with T2D in Han Chinese individuals.</p

Exome Array Association Results.

<p>The y axis represents the–log₁₀ (p-value) and the x axis is variant positions by chromosome. Genome-wide and suggestive statistical significance thresholds are illustrated by the two dotted lines.</p

Haplotypes association results across <i>MUC5B</i>.

<p>the y axis represents–log₁₀ (p values) and the x axis shows position within <i>MUC5B</i>. Red dotted lines indicate the Bonferroni correction level (-log₁₀ (0.05/1,553)), Points above the line are odds ratio values > 1, and below are odds ratio values < 1. Green dotted lines indicate the positions of significantly associated SNPs in single SNPs analyses. The “*” symbol by the SNP label indicates rare variants (MAF ≤ 0.0162). The LD heat map presents pairwise r² values within <i>MUC5B</i> based on the CADM study.</p