Fig. 7
Examples of ASM index SNPs in strong LD or precisely coinciding with GWAS peaks. a Map of the ASM DMR tagged by index SNP rs4487645, coinciding with a GWAS peak SNP for multiple myeloma (p = 3.0 × 10−14; OR = 1.38) and AL amyloidosis (p = 2.0 × 10−9; OR = 1.35). The ASM index SNP is in an enhancer region (yellow-coded chromatin state; GM12878 track) of the DNAH11 gene on chromosome 7. This SNP disrupts a PAX5_disc3 TF binding motif on the ALT allele. The REF allele, with intact high-affinity motif, is relatively hypomethylated. Additional motifs are in Additional file 3: Table S2. b Map of the ASM region tagged by index SNP rs2664280, in strong LD with GWAS peak SNPs rs2675662 for psoriasis (p = 3.0 × 10−8; OR = 1.14) and rs2633310 for T2D (p = 2.0 × 10−8; beta = − 0.044). The ASM index SNP is in an enhancer region (yellow-coded; GM12878) in the CAMK2G gene on chromosome 10. This SNP disrupts AP1 binding motifs (JUNB shown) on the ALT allele, with higher binding affinity on the REF allele, which is relatively hypomethylated. The motif maps to the negative strand and is reported 3′ to 5′. Additional motifs are in Additional file 3: Table S2. c Map of the ASM regions tagged by rs2853677 and rs6420020 index SNPs in the TERT gene on chromosome 5. The DMRs are in quiescent/repressed chromatin in most ENCODE samples (light and dark gray; K562 track), but this region is transcribed in undifferentiated H1-hESC. ASM for these DMRs was found only in GBMs. The index SNP rs2853677 is a GWAS peak SNP for non-small cell lung cancer and benign prostatic hyperplasia (p < 10−999; OR = 1.41 and p = 2.0 × 10−22; OR = 1.12, respectively). The other ASM index SNP, rs6420020 is in LD with GWAS peak SNPs for GBM (p = 6.0 × 10−24; OR = 1.68), breast carcinoma (p = 3.0 × 10−8; OR = 1.07), and chronic lymphocytic leukemia (p = 6.0 × 10−10; OR = 1.18). ASM allele switching is seen at rs6420020; polymorphic TF binding motifs are in Additional file 3: Table S2. d ASM DMR tagged by multiple SNPs (rs114627468, rs9357065, rs1225618, and rs1150668) in the promoter region of the ZNF192P1 pseudogene, flanked by coding genes in the ZSCAN family, on chromosome 6. ASM index SNP rs1150668 is a GWAS peak SNP for body height (p = 2.0 × 10−7; beta = − 0.060), smoking status (p = 6.0 × 10−15; beta = − 0.0086), smoking behavior (p = 3.0 × 10−8; beta = + 0.011), myopia (p = 1.0 × 10−11; beta = + 0 6.78), and schizophrenia with autism spectrum disorder (p = 8.0 × 10−11; OR = 1.07). In addition, the 4 ASM index SNPs are in a stringently defined haplotype block containing GWAS peak SNP rs62620225, for psychiatric phenotypes including well-being spectrum (p = 6 × 10− 12; beta = 0.023). ASM in this DMR was observed in multiple tissues, including brain. The ASM index SNP rs1225618 is as an ASB SNP for TAF1; other ASM-correlated motifs disrupted by the index SNPs are in Additional file 13: Table S12. Further examples of disease-linked ASM loci are in Additional files 11: Table S10, Additional files 12: Table S11-Additional files 13: Table S12, and Additional file 2: Figure S7-S9, S22, and S23.