Inheritance model^# selected with the AIC.

#<p>Models (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>): “-” = null, basic, “sub” = subset, “inv. sub” = inverse subset, general.</p>∧<p>Migraine characteristics: aura, pulsation, unipain ( = unilateral pain), sound ( = phonophobia), light ( = photophobia), duration of 4–72 hours ( = longdur), nausea, aggravation by physical activity ( = aggrphys), severity inhibits daily activities ( = inhibit), ≥6 attacks/year ( = freq).</p><p>“*” indicates models with significant LLR test p-values (<0.05) after adjustment for multiple hypothesis testing (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>).</p

WGHS active migraineurs (N = 3,003^*) with aura or migraine characteristic.

<p>*An additional 2,119 WGHS participants reported prior but not active migraine compared with 18,172 WGHS participants reported never experiencing migraine.</p

Estimates (beta coefficients) for association in the WGHS from logistic models for each of the 12 candidate SNPs as predictors of migraine accompanied by aura or other characteristics (black bars), or not (gray bars).

<p>Significant associations are indicated with “*” (see also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#pgen.1004366.s005" target="_blank">Table S4</a>). Model selection results (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#pgen-1004366-t003" target="_blank">Tables 3</a> & <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#pgen-1004366-t004" target="_blank">4</a>) are indicated with outlines around each plot as follows: Non-null models selected using the BIC are indicated with a heavy red outline, while non-null models selected using the AIC are indicated with a thin black outline. “Subset” or “inverse subset” models (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>) are indicated with a solid outline, “basic” models are indicated with a dotted outline, and “general” models are indicated with a dashed outline. Migraine characteristics considered were aura, pulsating pain ( = pulsate), unilateral pain ( = unipain), phonophobia ( = sound), photophobia ( = light), duration of 4–72 hours ( = longdur), nausea, aggravation by physical activity ( = aggrphys), inhibition of daily activities ( = inhibit), ≥6 attacks/year ( = freq). The rightmost column (actmig) indicates association estimates for active migraineurs, irrespective of status for the characteristics (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>). The order of SNPs is derived from clustering as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#pgen.1004366.s001" target="_blank">Figure S1</a>. See also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>.</p

Inheritance model^# selected with the BIC.

#<p>Models (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>): “-” = null, basic, “sub” = subset, “inv. sub” = inverse subset.</p>∧<p>Migraine characteristics: aura, pulsation, unipain ( = unilateral pain), sound ( = phonophobia), light ( = photophobia), duration of 4–72 hours ( = longdur), nausea, aggravation by physical activity ( = aggrphys), severity inhibits daily activities ( = inhibit), ≥6 attacks/year ( = freq).</p><p>“*” indicates models with significant LLR test p-values (<0.05) after adjustment for multiple hypothesis testing (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004366#s4" target="_blank">Methods</a>).</p

Genome-wide association studies of cardiometabolic phenotypes and inflammation.

<p>Abbreviations: BMI, body mass index; CAD, coronary artery disease; CARDIoGRAMplusC4D, Coronary Artery Disease Genome-wide Replication and Meta-Analysis plus Coronary Artery Disease Genetics Consortium; CHARGE, Cohorts for Heart and Aging Research in Genomic Epidemiology; CRP, c-reactive protein; DBP, diastolic blood pressure; DIAGRAM, DIAbetes Genetics Replication And Meta-analysis; FG, fasting glucose; FI, fasting insulin; GIANT, Genetic Investigation of ANthropometric Traits; GLGC, Global Lipids Genetic Consortium; HDLC, HDL-cholesterol; ICBP, International Consortium for Blood Pressure; LDLC, LDL-cholesterol; MAGIC, Meta-Analyses of Glucose and Insulin-related traits Consortium; SBP, systolic blood pressure; T2D, type 2 diabetes; TC, total cholesterol; TG, triglycerides.</p><p>Genome-wide association studies of cardiometabolic phenotypes and inflammation.</p

Biological and mediated pleiotropy of overlapping loci among inflammation and cardiometabolic phenotypes.

<p>Overlapping loci among inflammation and cardiometabolic phenotypes and type of pleiotropy according to the additional analyses. We identified six overlapping loci with mediated pleiotropic effects on CRP (left) and seven with a biological pleiotropic effect (right).</p

Quantile-quantile plots of CRP SNPs in cardiometabolic GWAS.

<p>QQ-plots were used to evaluate whether SNPs that are genome-wide significant associated with CRP, were in the cardiometabolic GWAS distributed differently from what is expected under the null-hypothesis. The observed p-values (dotted line) for the phenotypes HDL-cholesterol, fasting glucose, type 2 diabetes and coronary artery disease deviated significantly leftwards indicating that these p-values are smaller than expected under null hypothesis.</p

The association of known loci for cardiometabolic traits with serum CRP.

<p>^a Effect represents 1-unit change in the natural log-transformed CRP (mg/L) per copy increase in the risk allele. SE, standard error.</p><p>^b A1 and A2 represent respectively the risk allele and non-risk allele.</p><p>^c Top-SNP represents the SNP with the lowest p-value in the genomic region in the CRP meta-analysis. If the top-SNP is “The same”, the top SNP for the cardiometabolic traits is the same as the SNP with the lowest p-value in the CRP meta-analysis.</p><p><i>Note</i>: p-value ≤ 1.1×10^-4 is considered as study-wide significant (0.05/463)</p><p>Abbreviations: BMI, body mass index; CAD, coronary artery disease; FG, fasting glucose; FI, fasting insulin; HDLC, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; T2D, type 2 diabetes; TC, total cholesterol; TG, triglycerides.</p><p>The association of known loci for cardiometabolic traits with serum CRP.</p

P-values for the associations of the 18 CRP SNPs with different cardiometabolic phenotypes.

<p>P-values for the associations between the 18 CRP SNPs and BMI, lipids, glycemic phenotypes, SBP and coronary artery disease. The genes on the x-axis represent the genes in which the CRP SNPs are located or closest by. The numbers on the y-axis indicate the p-values of the association between the SNPs and the cardiometabolic phenotypes. Significant associations are colored as depicted in the figure legend. For BMI and SBP, no significant associations were observed. CAD, coronary artery disease; FG, fasting glucose; FI, fasting insulin; HDLC, HDL-cholesterol; LDLC, LDL-cholesterol; T2D, type 2 diabetes; TC, total cholesterol; TG, Triglycerides.</p

Quantile-quantile plot of cardiometabolic SNPs in CRP GWAS.

<p>QQ-plot was used to evaluate whether SNPs that are genome-wide significant associated with the cardiometabolic phenotypes, were in the CRP GWAS distributed differently from what is expected under the null-hypothesis. The observed p-values (dotted line) for the phenotypes deviated significantly leftwards indicating that these p-values are smaller than expected under null hypothesis.</p