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