HLA associations with cervical cancer histopathological type, and HPV genotype, for alleles scoring <i>P<</i>0.005 in at least one sub-analysis.

<p>HLA associations with cervical cancer histopathological type, and HPV genotype, for alleles scoring <i>P<</i>0.005 in at least one sub-analysis.</p

Conditional logistic regression analysis of imputed HLA alleles for the overall dataset for alleles scoring <i>P<</i>10⁻⁵ in either the primary analysis or after conditioning on stated variants.

<p>Conditional logistic regression analysis of imputed HLA alleles for the overall dataset for alleles scoring <i>P<</i>10⁻⁵ in either the primary analysis or after conditioning on stated variants.</p

Characteristics of cervical neoplasia cases in participating study populations following quality control steps.

<p>Characteristics of cervical neoplasia cases in participating study populations following quality control steps.</p

Accuracy of HLA typing by imputation compared with directly genotyped findings at two–and four-digit resolution.

<p>Accuracy of HLA typing by imputation compared with directly genotyped findings at two–and four-digit resolution.</p

Pairwise linkage disequilibrium (<i>r</i>²) plot of HLA alleles associated with cervical cancer.

<p>HLA alleles have been clustered according to their pairwise linkage disequilibrium on both the x- and y-axes. On the left-hand y-axis they are labelled as to whether they are risk or protective alleles in the overall cervical cancer dataset, and on the top x-axis according to whether they are HLA Class I or II alleles.</p

Zoom plot of the MHC showing association with cervical neoplasia.

<p>SNP associations are reported as filled-in dots, HLA amino-acid associations as hollow diamonds (<i>P</i>-values are for omnibus test of association at specific amino-acid positions). Colours represent extent of linkage disequilibrium with the HLA amino-acid(s) or SNP stated in the figure. (A) The linkage disequilibrium with amino acids at positions 13 and 71 that form part of the p4-pocket of HLA-DRB1. Reading from the p-telomere the HLA loci at which amino-acid constituents have been imputed are <i>HLA-A</i>, <i>-C</i>, <i>-B</i>, <i>-DRB1</i>, <i>-DQA1</i>, <i>-DQB1</i>, <i>-DPA1</i> and–<i>DPB1</i>. Allele-specific HLA type associations are given in the right hand plot. (B) Cervical neoplasia MHC association results having conditioned on amino acid positions 13 and 71 in HLA-DRB1. Linkage disequilibrium with the next largest association amino acid position 156 at HLA-B is shown. (C) Cervical neoplasia MHC association results having conditioned on amino acid positions 13 and 17 in HLA-DRB1 and 156 in HLA-B. No significant association remains.</p

Manhattan plot of genome-wide association study of cervical neoplasia.

<p>Manhattan plot of genome-wide association study of cervical neoplasia.</p

Conditional logistic regression analysis of imputed HLA amino acids at HLA-B position 156 (B_156), HLA-DRB1 position 13 (DRB1_13) and 71 (DRB1_71).

<p>Conditional logistic regression analysis of imputed HLA amino acids at HLA-B position 156 (B_156), HLA-DRB1 position 13 (DRB1_13) and 71 (DRB1_71).</p

Positive and negative predictive values for cervical neoplasia for centiles of genetic risk scores.

<p>Error Bars denote 2 standard deviations based on 10-fold cross validation.</p

Additional file 1: Table S1. of Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese

Detailed information of samples. Table S2. Analysis of rare coding variants. Table S3. Description and summary of quality control steps of whole-exome sequencing samples. Table S4. Exome sequencing coverage in genes included in the WES analyses. Table S5. Gene-based SKAT-O association test p-values and per gene counts of WES variants that passed filtering steps. Table S6. Gene-based Cochran–Mantel–Haenszel association test results based on WES variant counts in Chinese and Europeans. Table S7. Previously reported variants that are likely causal for ALS identified in individuals in our study. Table S8. NEK1, SOD1, TBK1 variants identified in SKAT-O and/or ALS specific variant/gene testing. Table S9. Not previously reported variants of probable/possible/unknown significance in ALS-related genes identified in at least one individual in our study. Table S10. Individuals identified with two or more variants considered relevant for ALS (oligogenic). Table S11. Previously reported variants that are unlikely causal (due to high minor allele frequency) identified in individuals in our study. (XLSX 7252 kb