Table 1.
Findings from TDT-based GWAS by Neale et al. (2008a), including genes in or near which the association finding is present as well information regarding the role of the gene and its possible involvement in psychiatric disorders
| SNP | OR | P value | Chr | Position (bp) | Position | Gene functiona | Additional remarks |
|---|---|---|---|---|---|---|---|
| rs2295426 | 0.7103 | 1.00E-05 | 14 | 58446208 | Intergenic | ||
| rs9676447 | 2.078 | 1.01E-05 | 19 | 54116059 | Intron of NUCB1 | Nucleobindin 1, function unknown, expression in multiple organs, including brain, family member NUCB2 encodes a satiety molecule that is associated with melanocortin signaling in the hypothalamus (Oh et al. 2006) |
Site is known for CNVs Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs2311120 | 0.6795 | 1.22E-05 | 18 | 50628121 | Approximately 20 kb upstream of RAB27B | Rabs are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking. RAB27B is primarily expressed in testis, but also found in brain. SNP is present in schizophrenia linkage region (Maziade et al. 2005) | |
| rs964647 | 1.717 | 1.34E-05 | 6 | 88993111 | Approximately 80 kb downstream of CNR1 | Encodes Cannabinoid receptor 1, highly expressed in brain and earlier found associated with alcohol and drug abuse and dependence (Zuo et al. 2007) and ADHD CNR1 has earlier been shown associated with ADHD (Lu et al. 2008; Ponce et al. 2003), present in region showing suggestive linkage to ADHD in meta-analysis (Zhou et al. 2008c) and a primary linkage analysis in ADHD (Ogdie et al. 2004) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs9389835 | 0.7307 | 1.58E-05 | 6 | 141312353 | Intergenic | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) | |
| rs876477 | 1.903 | 2.69E-05 | 4 | 20766026 | Intron of KCNIP4 | Encodes Kv channel interacting protein 4 isoform 3, a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), and may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The KCNIP4 protein also interacts with presenilin. Gene is also found among top-findings from GWAS in schizophrenia (Sullivan et al. 2008) and shows P values at 10−5 in GWAS in bipolar disorder (Sklar et al. 2008) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs6570426 | 0.735 | 2.74E-05 | 6 | 141239039 | Intergenic | Lies close to Schizophrenia linkage region (Lerer et al. 2003), with some evidence for nearby linkage region from a primary study in adult ADHD (Romanos et al. 2008) and the ADHD linkage meta-analysis (Zhou et al. 2008c) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs1539549 | 0.7305 | 2.88E-05 | 13 | 35349881 | Intron of DCLK1 = DCAMKL1 | Encodes doublecortin and CaM kinase-like 1, a microtubule-associated protein with microtubule polymerizing activity. Predominantly expressed in fetal and adult brain | |
| rs9484448 | 0.7385 | 2.94E-05 | 6 | 141260753 | Intergenic | Lies close to schizophrenia linkage region (Lerer et al. 2003), with some evidence for nearby linkage region from a primary study in adult ADHD (Romanos et al. 2008) and the ADHD linkage meta-analysis (Zhou et al. 2008c) | |
| rs7657608 | 1.356 | 2.96E-05 | 4 | 168390756 | Intron of SPOCK3 | Encodes a member of a novel Ca(2+)-binding proteoglycan family, a component of the extracellular matrix, high expression in brain, especially the caudate nucleus | |
| rs9608617 | 1.376 | 2.96E-05 | 22 | 26236244 | Intergenic | Lies within schizophrenia linkage region reported in meta-analysis (Lewis et al. 2003) | |
| rs6657749 | 0.6643 | 2.99E-05 | 1 | 212643136 | Intron of PTPN14 | Encodes a brain-expressed member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Gene shows P values at 10−4 in GWAS in bipolar disorder (Sklar et al. 2008) | |
| rs17722514 | 1.648 | 3.14E-05 | 13 | 89511946 | Intergenic |
Site is known for CNVs. Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
|
| rs1427324 | 0.7236 | 3.50E-05 | 14 | 58434446 | Intergenic | ||
| rs11221064 | 1.439 | 3.89E-05 | 11 | 127192523 | Intergenic | Close to schizophrenia linkage region reported in meta-analysis (Lewis et al. 2003) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs6919857 | 0.749 | 4.79E-05 | 6 | 137182147 | Within 5 kb upstream of PEX7 and 27 kb downstream of MAP3K5 | PEX7 encodes peroxisomal biogenesis factor 7, the cytosolic receptor for a set of peroxisomal matrix enzymes. MAP3K5 encodes a member of the MAPK pathway, that might be involved in apoptotic regulation in the brain | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs12772737 | 0.7246 | 4.96E-05 | 10 | 116731491 | Within 6 kb downstream of TRUB1 | Encodes TruB pseudouridine (psi) synthase homolog 1, expressed in many tissues, including brain, which may be responsible for synthesis of pseudouridine from uracil in tRNAs | |
| rs17754282 | 1.441 | 4.97E-05 | 11 | 87622650 | Intergenic | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) | |
| rs7187223 | 0.4458 | 5.21E-05 | 16 | 81015234 | Intergenic, within 203 kb upstream from CDH13 | Encodes cadherin 13, a member of the cadherin superfamily. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein. This particular cadherin is a putative mediator of cell–cell interaction in the heart and may act as a negative regulator of neural cell growth. Lies within the only significant linkage region for ADHD as determined in met-analysis (Zhou et al. 2008c). Has earlier shown association with metamphetamine dependence in GWAS (Uhl et al. 2008a). Gene is also found in GWAS in schizophrenia with P values at 10−4 (Sullivan et al. 2008) and shows CNVs potentially related to autism (Christian et al. 2008) | Most significant finding in quantitative GWAS by Lasky-Su et al. (2008b). Also shows association with adult ADHD in the GWAS by Lesch et al. (2008) |
| rs3782309 | 1.527 | 5.53E-05 | 12 | 26750663 | Intron of ITPR2 | Encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. Expression in many tissues, including brain. ITPR2 is involved in glutamate-mediated neurotransmission, is one of the main regulators of intracellular calcium concentrations, and has an important role in apoptosis. Shows association with amyotrophic lateral sclerosis (ALS) in GWAS (van Es et al. 2007) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs1541665 | 0.6338 | 5.60E-05 | 5 | 170075495 | Intron of KCNIP1 | Encodes Kv channel interacting protein 1 isoform 2, a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), and may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Lies close to linkage region observed in several primary studies as well as a meta-analysis (Lewis et al. 2003). Gene is also found in GWAS in schizophrenia with p-values at 10−4 (Sullivan et al. 2008) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs12505502 | 1.303 | 5.62E-05 | 4 | 91787046 | Intron of MGC48628 | Hypothetical gene/protein. Highly expressed in cerebellum, expression also in other parts of the brain and tissues. Gene is also found in GWAS in bipolar disorder with P values at 10−5 (Wellcome Trust Case Control Consortium 2007) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs922781 | 1.315 | 5.62E-05 | 15 | 58857636 | Intron of RORA | Encodes a member of the NR1 subfamily of nuclear hormone receptors. It can bind either as a monomer or as a homodimer to hormone-response elements upstream of several genes to enhance the expression of those genes. The specific functions of this protein are not known, but it has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. Close to suggestive linkage region for ADHD (Faraone et al. 2008). Gene is also found in GWAS in schizophrenia with p-values at 10−4 (Sullivan et al. 2008) | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs4241112 | 0.7214 | 6.06E-05 | 2 | 122378682 | Intergenic | Within and close to schizophrenia linkage regions (Lewis et al. 2003). | Also shows nominal association (P < 0.05) in quantitative GWAS by Lasky-Su et al. (2008b) |
| rs2678787 | 0.7228 | 6.36E-05 | 18 | 26436326 | Intergenic | Site is known for CNVs |
aWhere not indicated otherwise, the information is derived from the UCSC Browser, NCBI’s OMIM, Gene and Unigene databases, and the Sullivan Lab Evidence Project website (location of SNP expanded by ±5 Mb for genome-wide linkage scans, ±5 kb for GWAS, microarray and CNV studies, and ±50 kb for signposts)