Table 3.
Novel genomic loci associated with risk-taking propensity at a conditional false discovery rate <0.01 conditioning on association with bipolar disorder.
| SNP | Position | Nearest gene | Functional category | A1/A2 | beta risk | p risk | condFDR risk|BD | RegDB rank | CADD score | eQTL | Gene | Region |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rs1868402 | 2:68409037 | RP11-474G23.1:PPP3R1 | Intronic | A/G | −0.01 | 8.3E−07 | 3.6E−03 | 1f | 0.15 | Yes |
PNO1 PLEK |
Anterior cingulate, caudate, cerebellum Cerebellum |
| rs545200731 | 2:147644489 | AC062032.1 | ncRNA | T/C | 0.04 | 5.3E−06 | 5.8E−03 | 6 | 1.08 | No | – | – |
| rs34288552 | 2:171661486 | ERICH2 (6.0) | Intergenic | A/G | 0.01 | 2.0E−07 | 5.8E−03 | 5 | 7.33 | Yes |
ERICH2 |
Amygdala, anterior cingulate, cerebellum, cortex, frontal cortex, hypothalamus, susbtantia nigra Anterior cingulate, caudate |
| rs1014959 | 2:185472113 | ZNF804A | Intronic | A/G | −0.01 | 4.0E−05 | 8.3E−03 | 7 | 0.50 | No | – | – |
| rs326353 | 3:107853648 | RP11-861A13.4 | ncRNA | T/C | −0.01 | 6.0E−06 | 2.7E−03 | 3a | 3.28 | Yes |
IFT57 HHLA2 CD47 |
Whole blood Whole blood Whole blood |
| rs7628391 | 3:163680497 | RP11-208P4.1 (38.9) | Intergenic | T/C | 0.01 | 5.8E−06 | 4.0E−03 | 5 | 0.33 | No | – | – |
| rs4696294 | 4:152713089 | RP11-424M21.1 (7.6) | Intergenic | A/C | −0.01 | 2.9E−06 | 9.6E−03 | 6 | 0.02 | Yes |
SH3D19 RP11-164P12.5 FAM160A1 GATB RP11-164P12.3 FAM160A1 |
Caudate, cerebellum Cerebellum, whole blood Cerebellum, whole blood Cerebellum, cortex, frontal cortex, whole blood Cerebellum Cerebellum |
| rs76157183 | 5:145833478 | TCERG1 | Intronic | T/C | 0.02 | 5.1E−05 | 9.6E−03 | 5 | 0.08 | No | – | – |
| rs2195450 | 5:152871009 | GRIA1 | Intronic | A/G | 0.01 | 5.7E−06 | 3.8E−03 | 4 | 16.32 | No | – | – |
| rs852960 | 6:72205635 | RP1-288M22.2 (37.1) | Intergenic | A/G | 0.01 | 1.6E−05 | 5.7E−03 | 5 | 5.28 | No | OGFRL1 | Cerebellum |
| rs7758002 | 6:153440770 | RGS17 | Intronic | T/G | −0.01 | 7.1E−07 | 1.3E−03 | 7 | 1.06 | Yes |
MTRF1L RGS17 |
Anterior cingulate, cerebellum, whole blood Cerebellum |
| rs117450257 | 7:100446237 | SLC12A9:RP11-126L15.4 | ncRNA | A/G | −0.02 | 2.1E−05 | 5.6E−03 | 5 | 0.14 | No | – | – |
| rs80206917 | 7:140159389 | MKRN1 | Intronic | T/C | 0.01 | 2.3E−05 | 6.5E−03 | 2b | 5.92 | No | – | – |
| rs17055053 | 8:26088094 | RP11-98P2.1 (24.3) | Intergenic | T/C | −0.02 | 5.1E−05 | 9.5E−03 | 4 | 14.95 | No | – | – |
| rs7871821 | 9:128992756 | RP11-343J18.1 (39.6) | Intergenic | T/C | 0.01 | 5.5E−06 | 6.9E−03 | 5 | 1.18 | Yes | PBX3 | Cortex |
| rs7111300 | 11:45806624 | CTD-2210P24.4 (12.7) | Intergenic | T/G | 0.02 | 3.0E−05 | 7.0E−03 | 5 | 1.34 | Yes | CTD-2210P24.4 | Caudate, putamen |
| rs11827676 | 11:88263465 | GRM5 | Intronic | A/C | 0.01 | 3.7E−05 | 8.0E−03 | 6 | 3.66 | No | – | – |
| rs3885907 | 13:31314455 | ALOX5AP | Intronic | A/C | −0.01 | 6.7E−06 | 2.9E−03 | 4 | 2.17 | Yes | ALOX5AP | Whole blood |
| rs8005321 | 14:62458832 | SYT16 | Intronic | T/G | −0.01 | 4.2E−05 | 8.6E−03 | 4 | 0.33 | No | – | – |
| rs12927162 | 16:52684916 | CASC16 | ncRNA | A/G | −0.01 | 1.9E−06 | 4.9E−03 | 5 | 21.80 | No | – | – |
| rs72841389 | 17:61437939 | TANC2 | Intronic | A/G | 0.01 | 5.4E−06 | 4.7E−03 | 7 | 4.83 | Yes |
CYB561 TANC2 |
Anterior cingulate, caudate, cortex, frontal cortex, hippocampus, nucleus accumbens, putamen Cerebellum |
| rs6017733 | 20:44712815 | NCOA5 | Intronic | A/G | −0.01 | 2.2E−06 | 5.7E−03 | 6 | 6.25 | Yes | CD40 | Cerebellum |
The Table reports 22 novel independent genomic loci associated with risk-taking propensity conditioning on bipolar disorder at a condFDR < 0.01, after excluding loci associated with risk-taking propensity conditioning on SCZ or ADHD (Supplementary Table 6). The full list of significant loci is reported in Supplementary Table 5. 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 show the direction of effect of the A1 allele and p values from the original GWAS dataset. 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.