Cohort-wise effects of risk allele count on SBP.

<p>The higher median age in HBCS is reflected as higher systolic blood pressure (SBP) and less consistent association. Error bars show standard error.</p

2q33.1 and 5q23.2 loci cohort-wise ADVANCED model effect estimates and meta-analysis results with systolic blood pressure (SBP).^$

<p>Genomic positions are based on the human genome build 36. Alleles are reported on the forward strand of the reference genome. The effects are reported for the alleles increasing risk for IA in the Yasuno et al. studies <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002563#pgen.1002563-Yasuno1" target="_blank">[12]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002563#pgen.1002563-Yasuno2" target="_blank">[13]</a>. Risk alleles are aligned according to the forward strand of the reference genome. Minor allele frequencies (MAF) are based on from the HapMap Phase II CEU population data.</p>$<p>Diastolic blood pressure (DBP) and mean arterial pressure (MAP) association results from 2q33.1 and 5q23.2 SNP are in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002563#pgen.1002563.s005" target="_blank">Table S2</a>.</p>*<p>Meta SBP: meta-analysis of discovery and replication cohort p-values and beta for systolic blood pressure (SBP) with the ADVANCED model. Association analyses were corrected for gender, age, BMI, smoking habits and alcohol consumption.</p><p>SE: standard error.</p

Summary of leading SNPs from the 19 loci showing strong or suggestive association with IA in a multinational GWAS containing Finnish patients [12].

<p>Association results with intracranial aneurysm (IA) by Yasuno and colleagues are followed by our meta-analysis association results with systolic blood pressure (SBP), with the ROBUST and the ADVANCED models, respectively.</p><p>Table first shows association p-values with IA for the Finnish sub-group from the multinational GWAS (IA GWAS), followed by results from our meta-analysis of association with systolic blood pressure (SBP) with the ROBUST and ADVANCED models. In the ROBUST model of association we corrected for gender and age and in the ADVANCED model we further corrected for BMI, smoking habits and alcohol consumption.</p><p>Genomic positions are based on the human genome build 36. Alleles are reported on the forward strand of the reference genome. The effects are reported for the alleles increasing risk for IA in the Yasuno et al. studies <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002563#pgen.1002563-Yasuno1" target="_blank">[12]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002563#pgen.1002563-Yasuno2" target="_blank">[13]</a>. If SNP is intergenic, Gene represents the nearest gene. SNPs are directly genotyped unless otherwise marked (* HM2 imputed SNP, ** 1000G+HM3 imputed SNP). Yasuno et al (2011) at 8q24.23 followed-up with rs1554349 instead of the lead SNP, rs6577930.</p><p><b>In bold:</b> locus showing strongest association with SBP in meta-analysis.</p>#<p>‘IA GWAS’ triplet column shows the Finnish sub-group (n_{FINN-IA-CASES} = 912, n_{FINN-CONTROLS} = 8180) association results on IA of the GWAS by Yasuno and colleagues, except for the PPA results, which is not Finnish sub-group specific, but counted for the whole multinational cohort.</p>##<p>PPA: posterior probability of association with IA as calculated by Yasuno and colleagues for the multinational IA GWAS.</p>$<p>‘SBP meta-analysis with ROBUST model’ and ‘with ADVANCED model’ twin-columns show results of our candidate locus meta-analysis with SBP as the outcome variable. SBP meta-analysis beta values are given for IA risk alleles.</p><p>OR: odds ratio, CI: confidence interval, SE: standard error.</p

Meta-analysis results of 5q23.2 SNPs with systolic blood pressure from all four Finnish cohorts and ICBP-GWAS combined.

<p>Genomic positions are based on the human genome build 36. Risk alleles are aligned according to the forward strand of the reference genome. SE: standard error.</p

Summary of cohort characteristics.

<p>WG: whole-genome, QC: quality control, BP: blood pressure, SBP: systolic blood pressure, DBP: diastolic blood pressure, MAP: mean arterial pressure, PP: pulse pressure, BMI: body-mass index, SD: 1 standard deviation.</p

AJ individuals have higher CD polygenic risk score than NJ controls.

<p>NJ: non-Jewish; AJ: Ashkenazi Jewish; CD: Crohn’s disease; PRS: polygenic risk score. <b>A</b>) Density plot of CD polygenic risk scores in 454 AJ (green) and 35,007 NJ(purple)controls. AJ controls have higher CD polygenic risk score than NJ controls (0.97 s.d. higher, p<10⁻¹⁶). <b>B</b>) Density plot of CD polygenic risk scores in 1,938 AJ (green) and 20,652 NJ CD (purple) cases (0.54 s.d. higher, p<10⁻¹⁶). For both density plots the scores have been scaled to NJ controls, thus resulting in an NJ control PRS density of mean equal to 0 and variance equal to 1 (see Online Methods). <b>C</b>) Ranked (decreasing order) CD associated variants by estimated contribution to the differences in genetic risk between AJ and NJ. Associated variants with estimated contribution greater than or equal to 0.01, computed as 2 log(odds ratio) (AJ frequency—NJ frequency), assuming additive effects on the log scale, are highlighted in green. Associated variants with estimated contribution less than or equal to -0.01 are highlighted in purple. Forward slashes represent a break in variants highlighted.</p

Enrichment of alleles discovered in AJ exome sequencing project.

<p><b>A)</b> Histogram of estimated log enrichment statistic, defined as the log of the bias corrected odds ratio comparing the allele frequency in AJ population to the maximum allele frequency estimated from NFE, AFR, and AMR populations in ExAC. For each histogram bin we show a bar plot of the expected number of alleles belonging to the two groups we analyzed: 1) enriched (green) and 2) not enriched (white). <b>B)</b> Bar plots of estimated percentage of alleles belonging to the two groups we analyzed for all protein-coding (ALL), synonymous (SYN), protein-altering (PRA), and protein-truncating variants (PTV). An estimate of 34% of protein-coding alleles observed in AJ have a mean shift of 15-fold increased odds of the alternate allele compared to other reference populations. This observation is supported by the property that compared to intergenic variants, coding variants tend to be younger for a given frequency and the more pathogenic a variant, the younger it is, therefore tending to be population specific[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007329#pgen.1007329.ref013" target="_blank">13</a>].</p

Forty-eight ClinVar “pathogenic” alleles enriched in AJ.

<p>HGVS and Gene is the allele nomenclature in ClinVar and gene symbol, respectively. Enrichment odds ratio corresponds to the bias corrected comparison of allele frequency in AJ (AJ AF) to maximum frequency among three population groups (max EXAC AF): 1) NFE; 2) AMR; and 3) AFR. Curated trait is based on the trait description in the Online Mendelian Inheritance in Man (OMIM) and is independent of effect size as a Crohn’s risk allele. Inheritance corresponds to the inheritance description in OMIM (AR: autosomal recessive, AD: autosomal dominant, risk factor: not specified genetic risk factor). Alleles are sorted in decreasing order by AJ AF.</p