Table 2.
Identified SNPs for GERD (Chromosomes 7–22))
| Chr | SNP | BP | A1/A2 | OR [95% CI] | GERD adj. P | Meta | BE/EA P | Gene context | eQTL gene | PheWAS |
|---|---|---|---|---|---|---|---|---|---|---|
| 7 | rs4721096 | 1.8M | T/C | 0.96 [0.94–0.97] | 2.24 × 10−8 | --- | 0.020 | [MAD1L1]; AK127048, −7624; ELFN1, 89721 | BMI (1.1 × 10−12) | |
| 7 | rs10242223 | 3.5M | A/G | 1.04 [1.02–1.05] | 2.54 × 10−8 | +++ | 0.0040 | [SDK1]; DL490859, −28241 | SDK1 (4.7 × 10−8) | Smoking (2.2 × 10−8) |
| 7 | rs10228350 | 114M | A/T | 0.97 [0.96–0.98] | 3.87 × 10−8 | --- | 0.024 | [FOXP2] | FOXP2 (7.7 × 10−8) | MDD (3.3 × 10−9) |
| 7 | rs12706746 | 126M | G/A | 0.97 [0.95–0.98] | 1.98 × 10−8 | --- | 0.45 | [GRM8] | MDD (1.5 × 10−7) | |
| 11 | rs12792379 | 6M | G/A | 0.96 [0.95–0.98] | 3.91 × 10−8 | --- | 0.00023 | CCKBR, −23459; CNGA4, 2839 | CCKBR (5.0 × 10−12) | |
| 12 | rs11171710 | 56M | G/A | 0.97 [0.96–0.98] | 1.80 × 10−8 | --- | 0.078 | [RAB5B]; SUOX, −22964; CDK2, 1510 | RAB5B (1.4 × 10−26) | Obesity (3.3 × 10−9) |
| 12 | rs597808 | 112M | A/G | 1.03 [1.02–1.04] | 1.33 × 10−8 | +++ | 0.78 | [ATXN2]; BRAP, −106591; SH2B3, 83931 | Obesity (1.2 × 10−23) | |
| 17 | rs34796998 | 50M | C/G | 0.96 [0.95–0.97] | 2.98 × 10−11 | --- | 0.073 | CA10, 72144 | MDD (7.2 × 10−6) | |
| 19 | rs1363119 | 18M | A/G | 1.04 [1.03–1.05] | 5.81 × 10−10 | +++ | 0.00032 | PGPEP1, −6598; LSM4, 10808 | ||
| 19 | rs12974777 | 19M | C/T | 1.04 [1.02–1.05] | 6.92 × 10−9 | +?+ | 0.0014 | [KLHL26]; CRTC1, −28761; TMEM59L, 36944 | ||
| 21 | rs1297211 | 16M | C/G | 1.03 [1.02–1.04] | 3.64 × 10−8 | +++ | 0.31 | NRIP1, −4599 | NRIP1 (3.2 × 10−5) | Obesity (7.5 × 10−7) |
| 21 | rs7282609 | 34M | A/G | 0.97 [0.95–0.98] | 4.18 × 10−8 | --- | 0.077 | OLIG2, −119058; C21orf62, 93104 | EDU (1.4 × 10−7) |
Chr: (chromosome) and bp: base-pair position of SNP in hg19; A1/A2 refers to the effect allele and noneffect allele for the SNP; OR: GERD meta-analysis odds ratio and 95% confidence interval (confidence intervals were inflated by the square root of the LD-score regression intercept to account for potential residual stratification); GERD adj. P: adjusted P-value of SNP association in meta-analysis of UKBB, i.e., each SNP’s chi-squared value was divided by the intercept (1.04) from LD-score regression. 23andMe and QSkin for GERD; The column “Meta” shows the direction of risk association for the effect allele in order of the UKBB, 23andMe and QSkin GERD GWASs where “+” denotes increased risk, and “-” denotes decreased risk and “?” denotes that the result is missing for that study. P-value BE/EA shows P-value of SNP association for analysis of BE/EA samples. The “Gene context” column refers to the genes nearby (<200 kb) the most associated GERD SNP; brackets indicate that the peak SNP or those in LD (r2 > 0.8) are within the specified genes. The “-” sign after the genes indicates that the genes are located upstream of the top SNP, while the “+” after genes shows that the genes are located downstream of the top SNP. If any gene in the column has significant eQTL-association with the SNP from any of the 44 GTEx Tissues (https://gtexportal.org/), the gene is shown in eQTL column and the P-value quoted describes the strength of the relationship to the corresponding SNP. GWAS results for BMI, obesity, education, major depression, height and smoking were retrieved from https://genetics.opentargets.org, and are listed in the PheWAS column. More detailed eQTL and phewas results are in Supplementary Table 1. For each significant independent association a locuszoom plot is given in Supplementary Fig. 3 (note for rs12974777 the SNP shown is the top SNP in the region after conditioning on nearby SNP rs1363119).