Table 2.
Novel genomic loci associated bipolar disorder at a condFDR < 0.01 conditioning on association with risk-taking propensity.
| SNP | Position | Nearest gene (Kb) | Functional category | A1/A2 | Beta BD | p BD | condFDR BD|risk | RegDB rank | cadd score | eQTL | Gene | Region |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rs10917509 | 1:19992066 | HTR6 | UTR5 | T/C | 0.05 | 7.3E−08 | 5.2E−03 | 2b | 7.91 | Yes |
HTR6 NBL1 |
Nucleus accumbens, whole blood Nucleus accumbens |
| rs483252 | 1:108510358 | VAV3-AS1 | ncRNA | A/C | −0.06 | 9.9E−07 | 7.3E−03 | 3a | 5.74 | No | – | – |
| rs67050019 | 1:154267953 | RNU6-239P (0.03) | Upstream | A/G | 0.08 | 3.7E−07 | 4.5E−03 | 5 | 6.76 | No | – | – |
| rs4915346 | 1:199122192 | RP11-382E9.1 | ncRNA | A/G | −0.05 | 1.3E−05 | 6.6E−03 | 5 | 11.13 | No | – | – |
| rs4972439 | 2:175261443 | SCRN3 | Intronic | T/C | 0.06 | 4.3E−07 | 8.0E−03 | 4 | 1.50 | Yes | SCRN3 | Whole blood |
| rs6433891 | 2:181969709 | AC068196.1:AC104820.2 | ncRNA | A/G | 0.05 | 1.6E−07 | 3.1E−03 | 4 | 13.00 | Yes | UBE2E3 | Cerebellum, whole blood |
| rs4676412 | 2:241553492 | CAPN10:GPR35 | Intronic | A/G | 0.06 | 7.6E−08 | 7.8E−03 | 4 | 0.11 | Yes | ANKMY1 | Cortex |
| rs7644022 | 3:10510618 | ATP2B2 | Intronic | A/C | 0.05 | 2.5E−07 | 6.2E−03 | 5 | 3.51 | No | – | – |
| rs78104110 | 3:114133266 | ZBTB20 | Intronic | T/C | −0.13 | 2.1E−07 | 1.4E−03 | 5 | 5.22 | No | – | – |
| rs2651566 | 4:101507968 | EMCN (68.1) | Intergenic | A/G | −0.04 | 4.3E−06 | 9.0E−03 | 7 | 2.23 | No | – | – |
| rs11770210 | 7:29993998 | SCRN1 | Intronic | A/G | 0.07 | 6.4E−08 | 8.6E−03 | 5 | 1.14 | Yes |
PLEKHA8 AC007285.6 WIPF3 SCRN1 |
Cerebellum, whole blood Cerebellum Cortex Whole blood |
| rs10869262 | 9:76102010 | RP11-404E6.1 (11.0) | Intergenic | A/G | 0.05 | 7.8E−08 | 9.0E−03 | 7 | 1.19 | Yes |
ANXA1 ALDH1A1 |
Whole blood Whole blood |
| rs75888683 | 12:79478068 | SYT1 | Intronic | T/G | 0.12 | 1.1E−07 | 6.3E−03 | 6 | 3.32 | Yes | SYT1 | Spinal cord |
| rs8043792 | 16:61660554 | CDH8 (20.6) | Intergenic | T/C | −0.04 | 2.0E−06 | 3.3E−03 | 6 | 4.88 | No | – | – |
| rs4788865 | 17:73115508 | ARMC7 | Intronic | T/G | −0.05 | 2.3E−07 | 6.8E−03 | 4 | 3.35 | Yes |
NUP85 NTC5 ITGB4 MRPS7 SUMO2 GGA3 |
Amygdala, anterior cingulate, caudate, cerebellum, cortex, hippocampus, hypothalamus, whole blood Nucleus accumbens, putamen, spinal cord hypothalamus Putamen Whole blood Whole blood Whole blood |
Novel independent genomic loci associated with bipolar disorder conditioning on risk-taking propensity at a condFDR < 0.01, after exclusion of loci associated with either SCZ (Supplementary Table 5) or ADHD (Supplementary Table 6) after conditioning on risk-taking propensity. The full list of significant loci is reported in Supplementary Table 3. Nearest gene and functional category have been annotated using FUMA (for SNPs located in intergenic regions, distance in Kb from the nearest gene is reported). Beta and p columns show the direction of effect of the A1 allele and p values from the original GWAS dataset. The RegBD rank (from 1 to 7, with 1 being associated with highest evidence of functional effects) was calculated using RegulomeDB based on known and predicted regulatory elements. The CADD score, which predicts how deleterious a variant is on protein structure/function was computed in FUMA. Higher scores indicate more deleterious SNPs, with a suggested threshold of 12.37 for a SNP to be considered deleterious. In case the SNP is reported to be a significant eQTL in GTEx v.8 in brain regions or whole blood, the last two columns report regulated genes and relative regions.