Table 2. Social responsiveness association in RASopathy top results.
The independent SNPs with social responsiveness score (SRS) association in RASopathy (random effects meta-analysis P < 1.0x10-4) are listed. The data underlying the top six candidate modifiers are graphically illustrated in S6 Fig. For each SNP, the following is listed in order of columns: SNP rsID, chromosome (CHR), position (BP, reference version hg19), minor allele frequency in the dataset (MAF), groups contributing to the RASopathy association (group with the most significant association P-value is listed first and groups with similar direction of effect are in parentheses), Cochran’s Q P-value for all four RASopathy groups, RASopathy (CFC, CS, NF1, and NS) SRS association (random effects meta-analysis) P-value, control sibling SRS P-value (linear regression), gene(s) containing or flanking SNP.
| SNP | CHR | BP | MAF | RASopathy | RASopathy heterogeneity P | RASopathy P | Sibling P | Nearest gene(s) |
|---|---|---|---|---|---|---|---|---|
| rs62621010 | 7 | 37,749,392 | 0.02 | NF1 (CS) | 3.7x10-7 | 5.6x10-7 | 0.87 | ELMO1 / GPR141 |
| rs531418 | 5 | 163,079,682 | 0.08 | NF1 (CFC, CS, NS) | 0.82 | 1.4x10-6 | 0.016 | MAT2B |
| rs11013152 | 10 | 23,137,611 | 0.26 | CS (CFC, NF1) | 1.0x10-4 | 1.8x10-6 | 0.82 | PIP4K2A |
| rs117802216 | 11 | 25,911,732 | 0.05 | NF1 (CFC, CS, NS) | 0.057 | 2.0x10-6 | 0.33 | LUZP2 |
| rs1028948 | 20 | 16,213,705 | 0.12 | CFC (CFC, CS, NF1, NS) | 0.66 | 2.1x10-6 | 0.84 | MACROD2 |
| rs149068014 | 11 | 118,639,179 | 0.01 | NF1 (CS, NF1) | 1.8x10-4 | 2.2x10-6 | 0.37 | DDX6 |
| rs6518584 | 22 | 19,821,819 | 0.44 | CS (CFC, NF1, NS) | 0.061 | 2.5x10-6 | 0.36 | GNB1L |
| rs11573662 | 9 | 110,063,197 | 0.14 | CS (CFC, NF1, NS) | 0.53 | 3.3x10-6 | 0.66 | RAD23B |
| rs117695738 | 15 | 100,630,815 | 0.05 | CS (CFC, NF1, NS) | 0.30 | 4.6x10-6 | 0.54 | ADAMTS17 |
| rs646770 | 13 | 103,325,307 | 0.33 | NF1 (CFC, CS, NS) | 0.076 | 4.8x10-6 | 0.92 | TPP2 |
| rs486955 | 10 | 104,546,284 | 0.13 | NS (CFC, CS, NF1) | 0.14 | 5.4x10-6 | 0.72 | WBP1L |
| rs12594951 | 15 | 42,934,631 | 0.46 | CS (CFC, NF1, NS) | 0.071 | 5.9x10-6 | 0.21 | STARD9 |
| rs2139219 | 4 | 165,979,548 | 0.04 | NF1 (CFC, CS, NS) | 0.017 | 6.0x10-6 | 0.067 | TMEM192 |
| rs4680721 | 3 | 29,413,623 | 0.12 | CFC (CS, NF1, NS) | 0.32 | 7.3x10-6 | 0.16 | RBMS3 |
| rs12209962 | 6 | 6,451,710 | 0.41 | CS (NF1, NS) | 3.3x10-5 | 1.2x10-5 | 0.26 | LY86 |
| rs12518526 | 5 | 77,621,049 | 0.49 | CFC (CS, NF1, NS) | 0.42 | 1.3x10-5 | 0.51 | AP3B1 / SCAMP1 |
| rs59627556 | 16 | 82,130,477 | 0.08 | NF1 (CFC, NS) | 0.031 | 1.3x10-5 | 0.88 | HSD17B2 |
| rs57626469 | 16 | 12,577,817 | 0.10 | CS (CFC, NF1, NS) | 0.041 | 1.3x10-5 | 0.50 | SNX29 |
| rs80270452 | 1 | 205,539,721 | 0.01 | NF1 (CFC) | 0.033 | 1.3x10-5 | 0.058 | MFSD4 |
| rs9518224 | 13 | 101,597,633 | 0.36 | CFC | 2.2x10-6 | 1.6x10-5 | 0.66 | NALCN |
| rs7962094 | 12 | 109,008,869 | 0.30 | CS (CFC, NF1, NS) | 0.22 | 1.7x10-5 | 0.21 | SELPLG |
| rs77503217 | 11 | 127,817,436 | 0.05 | NF1 (CS, NS) | 3.7x10-5 | 2.0x10-5 | 0.19 | KIRREL3 / ETS1 |
| rs75450294 | 11 | 97,570,766 | 0.03 | CFC (NF1, NS) | 0.39 | 2.0x10-5 | 0.74 | CNTN5 |
| rs112114585 | 12 | 119,209,797 | 0.04 | NF1 (CFC, CS, NS) | 3.4x10-3 | 2.1x10-5 | 0.90 | SUDS3 |
| rs75553973 | 7 | 42,656,800 | 0.02 | NF1 (CS, NS) | 0.95 | 2.1x10-5 | 0.71 | GLI3 |
| rs62221469 | 21 | 46,282,961 | 0.25 | CS (CFC, NF1) | 0.054 | 2.2x10-5 | 0.50 | PTTG1IP |
| rs73141393 | 12 | 70,832,093 | 0.06 | NS (CFC, CS, NF1) | 0.39 | 2.3x10-5 | 0.76 | KCNMB4 |
| rs6075577 | 20 | 19,809,524 | 0.47 | CFC (CS, NF1, NS) | 0.24 | 2.5x10-5 | 0.68 | SLC24A3 / RIN2 |
| rs117592064 | 10 | 90,787,531 | 0.02 | CFC (CS, NF1, NS) | 0.59 | 2.6x10-5 | 0.17 | FAS |
| rs79497225 | 12 | 19,703,676 | 0.02 | NF1 (CFC) | 0.022 | 2.8x10-5 | 0.89 | AEBP2 |
| rs11689566 | 2 | 118,966,616 | 0.06 | NF1 (CFC, CS, NS) | 0.26 | 2.8x10-5 | 0.34 | INSIG2 / EN1 |
| rs10463788 | 5 | 124,564,573 | 0.25 | NF1 (CFC, CS, NS) | 0.47 | 2.8x10-5 | 0.71 | ZNF608 / GRAMD3 |
| rs13026531 | 2 | 137,805,397 | 0.18 | NS (CS) | 1.5x10-6 | 3.0x10-5 | 0.10 | THSD7B |
| rs6516036 | 20 | 5,422,539 | 0.19 | CFC (CFC, CS, NF1, NS) | 0.51 | 3.1x10-5 | 0.78 | PROKR2 / GPCPD1 |
| rs11106988 | 12 | 93,734,450 | 0.47 | NS (CFC, CS, NF1) | 0.37 | 3.1x10-5 | 0.73 | EEA1 / NUDT4 |
| rs11527676 | 10 | 36,333,349 | 0.39 | NS (CFC, CS, NF1) | 0.41 | 3.2x10-5 | 0.48 | FZD8 / ANKRD30A |
| rs2874027 | 5 | 24,485,005 | 0.13 | CFC (CS, NF1, NS) | 0.35 | 3.3x10-5 | 0.38 | CDH10 |
| rs17634284 | 9 | 122,091,015 | 0.08 | NF1 (CFC, CS, NS) | 0.88 | 3.3x10-5 | 0.24 | BRINP1 |
| rs36081923 | 20 | 9,955,080 | 0.21 | CS (CFC, NF1, NS) | 0.91 | 3.4x10-5 | 0.82 | PAK7 / ANKEF1 |
| rs116261553 | 2 | 28,606,305 | 0.02 | NF1 (CFC, NS) | 0.031 | 3.6x10-5 | 0.77 | BRE / FOSL2 |
| rs1990743 | 17 | 63,943,956 | 0.44 | NF1 (CFC, CS, NS) | 0.14 | 3.7x10-5 | 0.35 | CEP112 |
| rs12827688 | 12 | 56,309,504 | 0.08 | NF1 (CFC, CS, NS) | 0.012 | 3.9x10-5 | 0.81 | WIBG |
| rs496957 | 15 | 46,875,541 | 0.19 | CFC (CFC, CS, NS) | 0.47 | 4.0x10-5 | 0.61 | SQRDL / SEMA6D |
| rs79448371 | 5 | 80,709,755 | 0.02 | NF1 (CFC, CS, NS) | 0.92 | 4.0x10-5 | 0.55 | ZCCHC9 / SSBP2 |
| rs6510032 | 19 | 57,487,513 | 0.09 | NF1 (CS) | 3.7x10-3 | 4.3x10-5 | 0.37 | USP29 |
| rs3807822 | 7 | 8,247,347 | 0.06 | NF1 (CFC, NS) | 0.059 | 4.3x10-5 | 0.02 | ICA1 |
| rs17834272 | 10 | 108,046,638 | 0.30 | CS (CFC, NF1, NS) | 0.47 | 4.5x10-5 | 0.82 | SORCS3 / SORCS1 |
| rs9519852 | 13 | 106,574,453 | 0.21 | CS (CFC, NF1, NS) | 0.85 | 4.7x10-5 | 0.76 | DAOA / EFNB2 |
| rs78471416 | 2 | 105,907,528 | 0.04 | NF1 (CS, NS) | 0.045 | 4.7x10-5 | 0.79 | TGFBRAP1 |
| rs10060705 | 5 | 63,901,304 | 0.49 | NS (CFC, CS, NF1, NS) | 0.23 | 4.7x10-5 | 0.73 | RGS7BP |
| rs545076 | 12 | 115,119,903 | 0.50 | CS (CFC, NF1, NS) | 0.38 | 4.9x10-5 | 0.89 | TBX3 |
| rs12634256 | 3 | 160,907,163 | 0.18 | NF1 (CFC, CS, NS) | 0.95 | 5.0x10-5 | 0.47 | B3GALNT1 / NMD3 |
| rs62323999 | 4 | 162,217,243 | 0.03 | NS (CFC, CS, NF1) | 0.76 | 5.3x10-5 | 0.43 | RAPGEF2 / FSTL5 |
| rs117872061 | 7 | 82,125,674 | 0.01 | NF1 (CFC, CS, NS) | 0.54 | 5.4x10-5 | 0.38 | CACNA2D1 / PCLO |
| rs76013032 | 1 | 108,421,826 | 0.04 | CFC (CS, NF1, NS) | 0.27 | 5.5x10-5 | 0.67 | VAV3 |
| rs7445190 | 5 | 63,911,811 | 0.28 | NS (CS, NF1) | 0.042 | 5.5x10-5 | 0.65 | RNF180 / FAM159B |
| rs4924250 | 15 | 38,675,052 | 0.09 | NF1 (CS) | 9.6x10-5 | 6.2x10-5 | 0.50 | SPRED1 / FAM98B |
| rs62245932 | 3 | 68,177,506 | 0.09 | CFC (CS, NF1, NS) | 0.51 | 6.2x10-5 | 0.65 | FAM19A1 |
| rs13112607 | 4 | 30,770,684 | 0.04 | NF1 (CFC, CS, NS) | 0.91 | 6.6x10-5 | 0.032 | PCDH7 |
| rs881122 | 11 | 117,972,936 | 0.23 | NF1 (CFC, CS, NS) | 0.52 | 6.7x10-5 | 0.15 | TMPRSS4 |
| rs35206247 | 16 | 7,112,749 | 0.13 | NF1 (CFC, CS, NS) | 0.027 | 6.8x10-5 | 0.44 | RBFOX1 |
| rs117101324 | 14 | 76,851,865 | 0.04 | NF1 (CFC, CS, NS) | 0.013 | 6.8x10-5 | 0.58 | ESRRB |
| rs2064049 | 21 | 16,938,815 | 0.18 | NS (CFC, CS, NF1) | 0.90 | 7.0x10-5 | 0.41 | NRIP1 / USP25 |
| rs72695575 | 4 | 167,648,687 | 0.04 | CFC (CS, NF1) | 0.15 | 7.2x10-5 | 0.18 | TLL1 / SPOCK3 |
| rs1477910 | 8 | 89,093,270 | 0.04 | NF1 (CS, NS) | 0.037 | 7.5x10-5 | 0.65 | MMP16 |
| rs11108403 | 12 | 96,483,815 | 0.15 | CS (CFC, NF1, NS) | 0.063 | 7.5x10-5 | 0.089 | LTA4H / ELK3 |
| rs78665078 | 4 | 47,060,825 | 0.03 | NF1 (CFC, NF1) | 3.8x10-4 | 7.6x10-5 | 0.85 | GABRB1 |
| rs12746755 | 1 | 232,014,313 | 0.01 | CS (CFC, NF1, NS) | 0.56 | 7.8x10-5 | 0.72 | DISC1 |
| rs17034964 | 4 | 157,531,487 | 0.31 | CS (CFC, NF1, NS) | 0.13 | 7.8x10-5 | 0.082 | CTSO / PDGFC |
| rs75082290 | 2 | 67,831,153 | 0.10 | CS (CFC, NF1, NS) | 0.25 | 7.9x10-5 | 0.037 | ETAA1 / C1D |
| rs73879235 | 3 | 170,626,704 | 0.03 | NF1 (CFC, CS, NS) | 0.81 | 8.1x10-5 | 0.96 | EIF5A2 |
| rs2762659 | 10 | 10,164,309 | 0.25 | CFC (CS, NF1, NS) | 0.91 | 8.2x10-5 | 0.49 | GATA3 / CELF2 |
| rs514614 | 18 | 362,173 | 0.50 | NF1 (CFC, CS, NS) | 0.56 | 8.2x10-5 | 0.24 | COLEC12 |
| rs73209085 | 3 | 194,253,965 | 0.04 | NS (CS, NF1) | 0.96 | 8.4x10-5 | 0.20 | U6 |
| rs73008243 | 6 | 144,394,296 | 0.08 | NF1 (CS) | 1.0x10-4 | 8.8x10-5 | 0.55 | PLAGL1/ SF3B5 |
| rs79877255 | 18 | 62,662,276 | 0.02 | NF1 (CFC, NS) | 0.24 | 9.0x10-5 | 0.84 | SERPINB8 / CDH7 |
| rs17728300 | 3 | 8,600,038 | 0.02 | NF1 (NS) | 3.8x10-5 | 9.1x10-5 | 0.76 | LMCD1 |
| rs16875506 | 5 | 77,788,791 | 0.34 | NS (CFC, CS, NF1) | 0.95 | 9.6x10-5 | 0.72 | LHFPL2 |
| rs2142967 | 1 | 209,711,015 | 0.06 | CFC (CS, NF1, NS) | 0.31 | 9.6x10-5 | 6.4x10-3 | CAMK1G / LAMB3 |
| rs3732209 | 2 | 128,079,806 | 0.31 | NS (NF1) | 6.6x10-4 | 9.8x10-5 | 0.18 | MAP3K2 |
| rs77320284 | 10 | 109,037,309 | 0.03 | NF1 (NS) | 7.2x10-4 | 1.0x10-4 | 0.27 | SORCS1 / XPNPEP1 |
| rs79534834 | 3 | 119,267,493 | 0.16 | NS (NF1) | 1.8x10-5 | 1.0x10-4 | 0.85 | CD80 |