Additional file 4 of Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights

Supplementary Table 1. Data and sample details of ASD and 8 genetically correlated traits (P < 0.05, calculated from LD Score Regression (LDSC)) are presented and applied towards multivariate-GWAS. Data from four excluded traits are additionally shown. Supplementary Table 2. 37 multivariate associations are identified with ASD as a central trait where 17/37, shown with asterisk are previously reported in the GWAS Catalog and in bold, 8 genes are identified as SFARI ASD genes. Supplementary Table 3. 19 gene regions/trait pairings passed coloc (Posterior Prob H4 > 90%, Shown in bold) called on coloc.abf with a window size of ± 50 KB flanking the SNP locus. Supplementary Table 4. (A) Mendelian randomization (MR) results for ASD as outcome and related traits. (B) MR where ASD is the exposure and related traits are the outcome. Supplementary Table 5. MV associated genes are found in systems curated/implicated with gut microbiome and neural systems from GeneCards. Supplementary Table 6. List of 637 Significant SNPs (p < 5e-8), with 315 already reported in the GWAS catalog, identified by MetaPhat multivariate-GWAS using ASD and 8 genetically correlated trait summary statistics. Supplementary Table 7. A) 108 enriched (p < 0.05) Go terms are annotated and (B) 46 pathways on WikiPathway C) KEGG D) Reactome resources e) Tissue from the list of multivariate ASD SNPs found enrichments in neuron and nervous systems related data. Supplementary Table 8. ASD central SNP alleles are mapped to GEMMA genotypes called from 112 (49% females) WGS samples (45 (42% females) ASD probands). Phi coefficients are calculated between allele proportions where Chi-square test is applied to assess statistical importance. Indicated with *. Fisher's exact test is applied when Chi-square assumptions are violated. Supplementary Table 9. eQTL and sQTL related results of the ASD central associations relative to brain and nervous systems from EBI QTL catalog are captured via https://fivex.sph.umich.edu/. Study URLs are listed at the bottom of the table.

补充表1。本表格呈现了自闭症谱系障碍（Autism Spectrum Disorder, ASD）及8个经连锁得分回归（LD Score Regression, LDSC）计算得到P<0.05的遗传相关性状的数据与样本细节，相关数据将应用于多变量全基因组关联分析（multivariate-GWAS）；此外还额外展示了4个被排除性状的数据。
补充表2。本研究以ASD为核心性状，共鉴定得到37个多变量关联信号，其中17/37（标注有星号）已在GWAS Catalog中报道，且以粗体标注；另有8个基因被鉴定为SFARI ASD基因。
补充表3。共有19个基因区域-性状配对通过共定位分析（coloc）筛选，其H4后验概率>90%（以粗体标注），该分析基于coloc.abf工具完成，窗口设置为单核苷酸多态性（Single Nucleotide Polymorphism, SNP）位点上下游±50 kb。
补充表4。(A) 以ASD为结局变量的相关性状孟德尔随机化（Mendelian randomization, MR）分析结果；(B) 以ASD为暴露变量的相关性状孟德尔随机化分析结果。
补充表5。经GeneCards数据库注释，多变量关联基因可归类至与肠道菌群及神经系统相关的人工整理标注系统中。
补充表6。本研究通过MetaPhat工具，结合ASD及8个遗传相关性状的汇总统计数据，共鉴定得到637个显著性SNPs（p<5e-8），其中315个已在GWAS Catalog中报道。
补充表7。(A) 共注释得到108个富集（p<0.05）的基因本体（Gene Ontology, GO）术语；(B) 46条WikiPathway通路、(C) 京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路、(D) Reactome通路，以及(E) 组织富集分析结果；上述富集分析均基于多变量ASD SNPs展开，结果显著富集于神经元及神经系统相关数据中。
补充表8。将ASD核心SNP等位基因映射至来自112例（女性占比49%）全基因组测序（Whole Genome Sequencing, WGS）样本的GEMMA基因型数据中，其中包括45例（女性占比42%）ASD先证者。计算等位基因频率间的Phi相关系数，并通过卡方检验评估统计学显著性，结果标注有星号；若卡方检验假设不成立，则采用Fisher精确检验。
补充表9。通过https://fivex.sph.umich.edu/ 工具，从欧洲生物信息学研究所（European Bioinformatics Institute, EBI）的QTL数据库中，提取得到与ASD核心关联相关的表达数量性状位点（expression Quantitative Trait Locus, eQTL）及剪接数量性状位点（splicing Quantitative Trait Locus, sQTL）分析结果，相关数据均针对大脑及神经系统；表格底部列出了本研究涉及的所有研究URL。