<i>NOS3</i> G894T genotype and allele frequencies stratified by race and diabetes case status.

<p>SNP, single nucleotide polymorphism; p¹, p-value Pearson’s chi-squared test for comparison of proportions of <i>NOS3</i> G894T genotypes; n, number.</p

Association of <i>NOS3</i> genotype and diabetes case status in whites stratified by obesity.

<p><i>NOS3</i>, endothelial nitric oxide synthase 3; n, number; OR, odds ratio; CI, confidence interval; p, p-value adjusted for age, sex, and field center; BMI, body mass index,</p>1<p>interaction term for <i>NOS3</i> G894 TT genotype and obesity;</p>**<p>reference genotype.</p

Clinical and demographic characteristics stratified by race and diabetes case status.

<p>p, p-value, significance of difference between group means determined by t-test; DBP, diastolic blood pressure; SBP, systolic blood pressure; HDL, high density lipoprotein; BMI, body mass index;</p>a<p>mean and standard deviation;</p>b<p>missing values (n = 1);</p>c<p>missing values (n = 2);</p>d<p>missing values (n = 5);</p>e<p>missing values (n = 4);</p>f<p>missing values (n = 12);</p>g<p>missing values (n = 15);</p>h<p>missing values (n = 16);</p>i<p>missing values (n = 21);</p>j<p>missing values (n = 20);</p>k<p>missing values (n = 55);</p>l<p>number and percentage;</p>*<p>p-value Pearson’s chi-squared test.</p

Additional file 1: of Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study

Top 100 CpGs from the epigenome-wide association study (EWAS) of WMH burden in ARIC African-Americans. Association P-value, effect size, and standard error for each probe are shown as well as location(chromosome, position) and probe type. (PDF 195 kb

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study

<div><p>Objective</p><p>We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ₄₂ concentrations and aβ₄₂:aβ₄₀ ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years).</p><p>Methods</p><p>Plasma aβ measures were linearly regressed onto age, gender, <i>APOE</i> ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested.</p><p>Results</p><p>Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in <i>KLKB1</i> (rs3733402; p = 4.33x10^-10) and <i>F12</i> (rs1801020; p = 3.89x10^-8) were significantly associated with midlife aβ₄₂ levels through cross-race meta-analysis; the <i>KLKB1</i> variant replicated internally using 1,014 additional participants with exome chip. <i>ITPRIP</i>, <i>PLIN2</i>, and <i>TSPAN18</i> were associated with the midlife aβ₄₂:aβ₄₀ ratio via the T5 test; <i>TSPAN18</i> was significant via the cross-race meta-analysis, whereas <i>ITPRIP</i> and <i>PLIN2</i> were European American-specific. <i>NCOA1</i> and <i>NT5C3B</i> were associated with the midlife aβ₄₂:aβ₄₀ ratio and the fold-change in aβ₄₂, respectively, via SKAT in African Americans. No associations replicated externally (N = 725).</p><p>Conclusion</p><p>We discovered age-dependent genetic effects, established associations between vascular-related genes (<i>KLKB1</i>, <i>F12</i>, <i>PLIN2</i>) and midlife plasma aβ levels, and identified a plausible Alzheimer’s Disease candidate gene (<i>ITPRIP</i>) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.</p></div

Variants contributing to the significant T5 gene-based tests.

<p>This figure depicts the single-variant model results for variants contributing to the T5 tests of <i>ITPRIP</i>, <i>PLIN2</i>, and <i>TSPAN18</i> on the third visit aβ₄₂: aβ₄₀ ratio. One isoform was drawn unless the regions harboring variants differed substantially. Each contributing variant is labeled by name, single-variant association p-value, and direction of the minor allele effect (in parentheses). Variants with nominal (p<0.05) levels of association are in red. Overlapping variants in the two racial groups are encapsulated by a red box.</p

<i>KLKB1</i> and <i>F12</i> single-variant associations in ARIC participants with exome sequence.

<p> Panel A shows boxplots of the third visit aβ₄₂ levels and the fold-changes in aβ₄₂ stratified by the rs3733402 genotype in EAs. Panel B depicts the relative frequencies of the rs1801020 genotypes within each aβ₄₂ (visit 3) tertile in AAs and EAs. The plotted values are inverse normal transformed amyloid values adjusted for age, gender, time between visits (fold-change aβ₄₂ only), and <i>APOE</i> ε4 carriage status.</p

Effects of carrying a minor allele in <i>TSPAN18</i>, <i>ITPRIP</i>, and <i>PLIN2</i> on the third visit aβ₄₂: aβ₄₀ ratio in EAs.

<p>The plotted values are the inverse normal transformed ratios adjusted for age, gender, and <i>APOE ε</i>4 carriage status.</p

Significant single-variant results.

<p>Significant single-variant results.</p

Variants contributing to the significant SKAT gene-based tests.

<p>This figure displays the single-variant model results for variants contributing to the SKAT tests of <i>NCOA1</i> and <i>NT5C3B</i> on the third visit aβ₄₂: aβ₄₀ ratio and fold-change in aβ_42, respectively. One isoform was drawn unless the regions harboring variants differed substantially. Each contributing variant is labeled by name, single-variant association p-value, and direction of the minor allele effect. Variants with nominal (p<0.05) levels of association are in red. Overlapping variants in the two racial groups are encapsulated by a red box.</p