Table1_Polygenic risk score predicts all-cause death in East Asian patients with prior coronary artery disease.docx

IntroductionCoronary artery disease (CAD) is a highly heritable and multifactorial disease. Numerous genome-wide association studies (GWAS) facilitated the construction of polygenic risk scores (PRS) for predicting future incidence of CAD, however, exclusively in European populations. Furthermore, identifying CAD patients with elevated risks of all-cause death presents a critical challenge in secondary prevention, which will contribute largely to reducing the burden for public healthcare.MethodsWe recruited a cohort of 1,776 Chinese CAD patients and performed medical follow-up for up to 11 years. A pruning and thresholding method was used to calculate PRS of CAD and its 14 risk factors. Their correlations with all-cause death were computed via Cox regression.Results and discussionWe found that the PRS for CAD and its seven risk factors, namely myocardial infarction, ischemic stroke, angina, heart failure, low-density lipoprotein cholesterol, total cholesterol and C-reaction protein, were significantly associated with death (P ≤ 0.05), whereas the PRS of body mass index displayed moderate association (P < 0.1). Elastic-net Cox regression with 5-fold cross-validation was used to integrate these nine PRS models into a meta score, metaPRS, which performed well in stratifying patients at different risks for death (P < 0.0001). Combining metaPRS with clinical risk factors further increased the discerning power and a 4% increase in sensitivity. The metaPRS generated from the genetic susceptibility to CAD and its risk factors can well stratify CAD patients by their risks of death. Integrating metaPRS and clinical risk factors may contribute to identifying patients at higher risk of poor prognosis.</p

Frequency of the <i>KIR</i> centromeric/telomeric alleles.

<p>Frequency of the <i>KIR</i> centromeric/telomeric alleles.</p

Association of <i>KIR/HLA</i> alleles with baseline HIV Log₁₀RNA.

<p>Association of <i>KIR/HLA</i> alleles with baseline HIV Log₁₀RNA.</p

Frequency of <i>KIR</i> alleles.

<p>Frequency of <i>KIR</i> alleles.</p

Baseline characteristics.

<p>Baseline characteristics.</p

Frequency of the <i>KIR/HLA</i> alleles.

<p>Frequency of the <i>KIR/HLA</i> alleles.</p

Association of <i>KIR/HLA</i> alleles with baseline CD4⁺ lymphocyte count.

<p>Association of <i>KIR/HLA</i> alleles with baseline CD4⁺ lymphocyte count.</p

Genome-Wide Scan Identifies Variant in <em>TNFSF13</em> Associated with Serum IgM in a Healthy Chinese Male Population

<div><p>IgM provides a first line of defense during microbial infections. Serum IgM levels are detected routinely in clinical practice. And IgM is a genetically complex trait. We conducted a two-stage genome-wide association study (GWAS) to identify genetic variants affecting serum IgM levels in a Chinese population of 3495, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Our data show that a common single nucleotide polymorphism (SNP), rs11552708 located in the <em>TNFSF13</em> gene was significantly associated with IgM levels (<em>p</em> = 5.00×10⁻⁷ in first stage, <em>p</em> = 1.34×10⁻³ in second stage, and <em>p</em> = 4.22×10⁻⁹ when combined). Besides, smoking was identified to be associated with IgM levels in both stages (<em>P</em><0.05), but there was no significant interaction between smoking and the identified SNP (<em>P</em>>0.05). It is suggested that <em>TNFSF13</em> may be a susceptibility gene affecting serum IgM levels in Chinese male population.</p> </div

Manhattan plot of genome-wide association analyses for IgM level.

<p>X-axis shows chromosomal positions. Y-axis shows −log10 p-values from the linear regression.</p

General characteristics of the two-stage GWAS study participants.

a<p><i>T</i>-test was used to compare means of the continuous variables between the first and the second stages.</p>b<p><i>X</i>²-test was used to compare the differences for categorical variables.</p