Association of LpPLA2 mass and activity with incident ischemic stroke.

<p>age, gender, race-ethnicity, education.</p><p>adjusted for age, sex, race-ethnicity, education, waist circumference, physical activity, moderate alcohol consumption, smoking status, diabetes mellitus, systolic blood pressure, coronary artery disease, Low density lipoprotein, High density lipoprotein.</p

Stratification by race ethnicity for all ischemic stoke.

<p>adjusted for age, sex, race-ethnicity, education, waist circumference, physical activity, moderate alcohol consumption, smoking status, diabetes mellitus, systolic blood pressure, coronary artery disease, Low density lipoprotein, High density lipoprotein.</p

Baseline characteristics according to race ethnicity.

<p>SD: standard deviation; IQR: interquartile range.</p><p>Hypertension defined as: history, taking medications, or systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg;</p><p>Moderate alcohol intake: 1 alcoholic drink per week to 2 drinks per day.</p><p>Kruskal Wallis test for continuous variables and Chi-Squared test for categorical variables.</p

Rare Variants in <i>NOD1</i> Associated with Carotid Bifurcation Intima-Media Thickness in Dominican Republic Families

<div><p>Cardiovascular disorders including ischemic stroke (IS) and myocardial infarction (MI) are heritable; however, few replicated loci have been identified. One strategy to identify loci influencing these complex disorders is to study subclinical phenotypes, such as carotid bifurcation intima-media thickness (bIMT). We have previously shown bIMT to be heritable and found evidence for linkage and association with common variants on chromosome 7p for bIMT. In this study, we aimed to characterize contributions of rare variants (RVs) in 7p to bIMT. To achieve this aim, we sequenced the 1 LOD unit down region on 7p in nine extended families from the Dominican Republic (DR) with strong evidence for linkage to bIMT. We then performed the family-based sequence kernel association test (famSKAT) on genes within the 7p region. Analyses were restricted to single nucleotide variants (SNVs) with population based minor allele frequency (MAF) <5%. We first analyzed all exonic RVs and then the subset of only non-synonymous RVs. There were 68 genes in our analyses. Nucleotide-binding oligomerization domain (<i>NOD1)</i> was the most significantly associated gene when analyzing exonic RVs (famSKAT p = 9.2x10^-4; number of SNVs = 14). We achieved suggestive replication of <i>NOD1</i> in an independent sample of twelve extended families from the DR (p = 0.055). Our study provides suggestive statistical evidence for a role of rare variants in <i>NOD1</i> in bIMT. Studies in mice have shown Nod1 to play a role in heart function and atherosclerosis, providing biologic plausibility for a role in bIMT thus making <i>NOD1</i> an excellent bIMT candidate.</p></div

Stratification by race ethnicity for large-artery atherosclerotic (LAA) stroke.

<p>adjusted for age, sex, race-ethnicity, education, waist circumference, physical activity, moderate alcohol consumption, smoking status, diabetes mellitus, systolic blood pressure, coronary artery disease, Low density lipoprotein, High density lipoprotein.</p

Association of LpPLA2 with large-artery atherosclerotic (LAA) stroke.

<p>Model 1; adjusted for demographics (i.e. age, gender, race-ethnicity, education).</p><p>Model 2; adjusted for demographics & medical risk factors (i.e. age, sex, race-ethnicity, education, waist circumference, physical activity, moderate alcohol consumption, smoker, diabetes mellitus, systolic blood pressure, coronary artery disease, LDL, HDL).</p

Gene-based association results for rare variant analyses in the chr 7p region, for genes with p<0.05 in at least one analysis.

<p>Gene-based association results for rare variant analyses in the chr 7p region, for genes with p<0.05 in at least one analysis.</p

Pedigree of Family 5987 depicting residual bIMT value and rs5743335 genotype, our most significantly associated variant in <i>NOD1</i>.

<p>Individuals with residual bIMT value ≤ 0 are shaded gray in the upper right quadrant and individuals with residual bIMT value > 0 are shaded completely gray.</p

Polymorphic variants identified by re-sequencing of 7p region in 9 discovery families.

<p>Polymorphic variants identified by re-sequencing of 7p region in 9 discovery families.</p

Characteristics of Dominican families included in analyses for chr7 analyses.

<p>Characteristics of Dominican families included in analyses for chr7 analyses.</p