Table 2.

Association findings from quantitative GWAS by Lasky-Su et al. (2008b) with P values <10⁻⁵, 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

Phenotype	SNP	Genetic model	P value	Chr	Base pairs	Position	Gene functiona	Additional remarks
FBAT-PC all symptoms	rs6565113	Additive	NA#	16	81665146	Intron of 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 of 10−4 (Sullivan et al. 2008) and shows CNVs potentially related to autism (Christian et al. 2008)	Gene also shows association with adult ADHD in the GWAS by Neale et al. (2008a) and Lesch et al. (2008)
	rs1018040	Additive	4.64E-06	1	216772437	Intergenic	Region lies close to linkage interval for anorexia nervosa (Devlin et al. 2002)
	rs1018040	Dominant	2.97E-06	1	216772437
	rs930421	Recessive	5.64E-06	2	42834743	Exon of MTA3	Encodes metastasis associated 1 family, member 3, a component of the nucleosome-remodeling and histone- deacetylase multiprotein complex (NuRD). MTA3 plays a role in maintenance of the normal epithelial architecture through the repression of SNAI1 transcription in a histone deacetylase-dependent manner, and the regulation of E-cadherin levels. Expressed in multiple tissues, including brain, especially cerebellum	Close to rs6719977 associated with FBAT-PC hyperactive–impulsive symptoms and rs10865184 showing association with ADHD symptom count in interaction with maternal criticism
	rs7577925	Dominant	2.55E-06	2	133756989	Intron of NAP5 (FLJ34870)	Encodes Nck-associated protein 5, a peripheral clock protein 2. Expressed in brain (especially cerebellum) and other tissues. Function unknown. Within schizophrenia linkage region observed in meta-analysis (Lewis et al. 2003)
	rs1350666	Additive	8.30E-06	4	75443454	Within 15 kb upstream of EREG	Encodes epiregulin, a member of the epidermal growth factor family, which can bind to the EGF receptor and may be a mediator of localized cell proliferation. As a mitogen it may stimulate cell proliferation and/or angiogenesis
	rs708188	Recessive	7.21E-06	12	28111983	Intergenic	Within 5 kb of genome-wide significant association for type 2 diabetes (Zeggini et al. 2007)
	rs522958	Recessive	1.03E-06	12	28119834	Intergenic
	rs1514928	Additive	3.05E-06	14	61748056	Within 110 kb downstream of SYT16	Encodes synaptotagmin XVI, which may be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent and expressed in brain	Site known for CNVs
	rs8047014	Additive	3.52E-06	16	67692550	Within 5 kb upstream of HAS3, within 20 kb downstream of TMCO7	HAS3 encodes hyaluronan synthase 3 isoform a, a protein involved in the synthesis of the unbranched glycosaminoglycan hyaluronan, or hyaluronic acid, which is a major constituent of the extracellular matrix. Expressed in brain and other tissues TMCO7 encodes transmembrane and coiled-coil domains 7, a protein of unknown function. Expressed in brain and other tissues Within linkage region for ADHD as identified in meta-analysis (Zhou et al. 2008c)
	rs260461	Dominant	8.38E-06	19	63462695	Within intron or 3’UTR of ZNF544	Encodes zinc finger protein 544, a zinc-regulated transcription factor expressed in brain and many other tissues
	rs130575	Additive	4.67E-06	22	33189793	Intergenic	Present in or near (suggestive) linkage regions for schizophrenia reported in meta-analysis (Lewis et al. 2003), for nicotine dependence (Saccone et al. 2007; Kelsoe et al. 2001)
	rs130575	Dominant	6.20E-06	22	33189793
FBAT-PC hyperactive-impulsive symptoms	rs1018040	Additive	8.20E-06	1	216772437	See above
	rs6719977	Additive	1.67E-06	2	42839307	Within 2 kb downstream of MTA3	Encodes metastasis associated 1 family, member 3, a component of the nucleosome-remodeling and histone-deacetylase multiprotein complex (NuRD). MTA3 plays a role in maintenance of the normal epithelial architecture through the repression of SNAI1 transcription in a histone deacetylase-dependent manner, and the regulation of E-cadherin levels. Expressed in multiple tissues, including brain, especially cerebellum	Close to rs930421 associated with FBAT-PC all symptoms and rs10865184 showing association with ADHD symptom count in interaction with maternal criticism
	rs6808138	Additive	5.38E-06	3	162875270	Intergenic		Site known for CNVs
	rs6808138	Dominant	8.21E-06	3	162875270
	rs41441749	Dominant	1.49E-06	6	18899702	Intergenic
	rs17641078	Additive	4.73E-06	9	1046959	In coding exon of DMRT2	Encodes doublesex and mab-3 related transcription factor 2, a potential regulator of sex differentiation. Expressed in multiple tissues, including brain. Falls into/close to suggestive linkage regions for autism (Allen-Brady et al. 2008; Szatmari et al. 2007b) and close to suggestive linkage region for nicotine dependence (Li et al. 2008)	Site known for CNVs
	rs17641078	Dominant	8.44E-06	9	1046959
	rs708188	Recessive	2.17E-06	12	28111983	See above
	rs522958	Recessive	7.59E-07	12	28119834	See above
	rs363512	Dominant	3.89E-06	21	29972688	In intron of GRIK1	Encodes glutamate receptor, ionotropic, kainate 1. Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. Earlier association studies suggest involvement of the gene in epilepsy en Parkinson’s disease (Lasky-Su et al. 2008b). Gene is also found in GWAS in bipolar disorder with P values at 10−4 (Wellcome Trust Case Control Consortium 2007)
FBAT-PC inattentive symptoms	rs552655	Dominant	n.a.#	6	13478466	Intron of GFOD1	Encodes glucose-fructose oxidoreductase domain containing 1 a gene expressed in brain and other tissues. The protein is predicted to be involved in electron transport and metabolic processes. Finding lies within linkage region for schizophrenia from meta-analysis (Lewis et al. 2003)
	rs4147141	Additive	7.90E-06	1	69351840	Intergenic
	rs4650135	Additive	5.45E-06	1	69457585	Intergenic
	rs4650135	Dominant	6.07E-06	1	69457585
	rs11786458	Additive	8.76E-06	8	40371858	Intergenic	Close to linkage region for schizphrenia (Stefansson et al. 2002)
	rs12679254	Recessive	2.08E-06	8	74436745	Within 10 kb of AK128216	Gene of unknown function
	rs11790994	Additive	2.47E-07	9	97469087	Intergenic	Within suggestive linkage region for ADHD in meta-analysis (Zhou et al. 2008c)
	rs10895959	Recessive	3.00E-06	11	105835372	Intergenic	Within suggestive linkage region for schizophrenia in meta-analysis (Lewis et al. 2003)
	rs478597	Additive	8.08E-06	12	116235808	Intron of NOS1	Encodes (neuronal) nitric oxide synthase 1. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter; it is implicated in neurotoxicity associated with stroke and neurodegenerative diseases and neural regulation of smooth muscle. NOS1 has recently shown association with traits related to impulsivity, including hyperactive and aggressive behaviors in adult ADHD, cluster B personality disorder, and autoaggressive and heteroaggressive behavior (Reif et al. 2009). Earlier, this gene was shown associated with Alzheimer’s disease and schizophrenia (Galimberti et al. 2008; Reif et al. 2006)
	rs17079773	Additive	4.71E-06	13	23496384	In intron of SPATA13	Encodes spermatogenesis associated 13, potentially involved in cell migration	Site known for CNVs
	rs17079773	Dominant	6.60E-06	13	23496384		Expressed in brain
	rs7495052	Recessive	2.83E-06	15	90353033	In intron of SLCO3A1	Encodes solute carrier organic anion transporter family, member 3A1, which might be involved in the regulation of extracellular vasopressin concentration in human brain and thus might influence the neuromodulation of neurotransmission by cerebral neuropeptides such as vasopressin. In/near suggestive linkage regions for autism (Szatmari et al. 2007b) and major depression (Holmans et al. 2004). Gene was associated with nicotine dependence at P values of 10−3 in locus-wide association study (Berrettini et al. 2008)
	rs17281813	Recessive	3.46E-06	16	48308291	In intron of ZNF423	Encodes zinc finger protein 423, expressed in multiple tissues including fetal brain and specifically in the substantia nigra, medulla, amygdala, thalamus, and cerebellum. Animal studies show that ZNF423 is required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures (Alcaraz et al. 2006). Close to suggestive linkage region for ADHD in meta-analysis (Zhou et al. 2008c)
	rs13330107	Recessive	8.50E-06	16	75436363	Intergenic	Within suggestive linkage region for ADHD in meta-analysis (Zhou et al. 2008c)	Site known for CNVs
Total ADHD symptom count	rs4147141	Additive	6.07E-06	1	69351840	See above
	rs272000	Recessive	9.10E-06	2	116372265	Within 50 kb downstream of DPP10	Encodes dipeptyl peptidase 10, which does not possess dipeptidyl peptidase activity but binds to specific voltage-gated potassium channels and alters their expression and biophysical properties. The expression of the gene is highest in brain. The finding lies within a linkage region for schizophrenia observed in meta-analysis and several primary studies (Lewis et al. 2003). In addition, the gene showed association in GWAS of schizophrenia (Sullivan et al. 2008) and bipolar disorder (Wellcome Trust Case Control Consortium 2007) at P = 10−5, and contains CNVs potentially linked to autism (Marshall et al. 2008)	Site known for CNVs
	rs17367118	Additive	8.69E-06	2	123358081	Intergenic	The finding lies within a linkage region for schizophrenia observed in meta-analysis (Lewis et al. 2003)
	rs1918172	Additive	5.18E-06	2	156596746	In intron of BC032407	Gene of unknown function
	rs11719664	Additive	2.48E-06	3	21930202	In intron of ZNF385D	Expression in many tissues including brain. The finding lies within a linkage region for schizophrenia observed in meta-analysis (Lewis et al. 2003) and a recent primary study (Irmansyah et al. 2008). The gene showed association in GWAS of bipolar disorder (Wellcome Trust Case Control Consortium 2007) at P values of 10−5	Site known for CNVs
	rs6791644	Recessive	8.32E-06	3	60746148	In intron of FHIT	Encodes a diadenosine 5′,5′′′-P1,P3-triphosphate hydrolase involved in purine metabolism. FHIT has a major role in regulating beta-catenin-mediated gene transcription. Expression in many tissues including brain. Gene is also found among top-findings from GWAS in schizophrenia (Sullivan et al. 2008) and is affected by CNVs in autism (Marshall et al. 2008; Sebat et al. 2007)
	rs17651978	Recessive	6.05E-06	3	71103180	In intron or 5′ UTR of FOXP1	Encodes Forkhead box protein P1, which belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. The gene shows universal expression. FOXP2, another family member is involved in developmental speech and language disorders and directly regulates targets related to neural development and synaptic plasticity and developmental disorders like autism and schizophrenia (Vernes et al. 2007, 2008). In addition, the gene showed association in GWAS of schizophrenia (Sullivan et al. 2008) at P = 10−5 and of bipolar disorder (Sklar et al. 2008) at P = 10−4
	rs2290416	Additive	8.51E-06	8	144728743	In coding exon of NAPRT1	Encodes nicotinate phosphoribosyltransferase domain containing 1, which is part of an enzymatic pathway that leads to production of nicotinamide adenine dinucleotide (NAD) from niacin (nicotinic acid), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress. Expression in many tissues including brain	Site known for CNVs
	rs10767942	Dominant	7.90E-06	11	32478583	Intergenic	The finding lies within/near linkage regions for autism (Duvall et al. 2007; Szatmari et al. 2007b; Trikalinos et al. 2006)
	rs7992643	Dominant	5.45E-06	13	99353039	Within 15 kb downstream of CLYBL	Encodes citrate lyase beta like protein of unknown function. Expression in many tissues including brain. The finding lies within/near linkage regions for bipolar disorder (Detera-Wadleigh et al. 1999) and schizophrenia (Blouin et al. 1998)
Hyperactive-impulsive symptom count	rs11590090	Recessive	2.51E-06	1	113115086	Within 60 kb downstream of FAM19A3	Encodes ‘family with sequence similarity 19 [chemokine (C–C motif)-like], member A3’. This gene is a member of the TAFA family which encode small secreted proteins. These proteins are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells (Tom et al. 2004). The finding lies within/near linkage regions for schizophrenia from primary and meta-analysis studies (Arinami et al. 2005; Lewis et al. 2003)	Site known for CNVs
	rs1202199	Dominant	8.52E-06	6	20264153	In intron of MBOAT1	MBOAT1 shares structural similarity with a superfamily of membrane-bound O-acetyltransferases that transfer organic compounds, usually fatty acids (e.g., cholesterol, diacylglycerol, palmitoyl), onto hydroxyl groups of membrane-embedded targets. By this way MBOAT1 is essential for membrane asymmetry and diversity. Expression in many tissues including brain. The finding lies within/near linkage regions for schizophrenia from meta-analysis (Lewis et al. 2003)
	rs7816032	Recessive	2.25E-06	8	19831171	Within 15 kb upstream of LPL	Encodes lipoprotein lipase, a protein which has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Expressed in many tissues including brain. Gene has shown association with many different lipid-related disorders
	rs8041675	Additive	3.98E-06	15	35129894	In intron of MEIS2	Encodes a homeobox protein belonging to the TALE (‘three amino acid loop extension) family of homeodomain-containing proteins. TALE homeobox proteins are highly conserved transcription regulators, and several members have been shown to be essential contributors to developmental programs. Expression in multiple tissues including brain. The finding lies within/near linkage region for ADHD from a primary study and meta-analysis (Bakker et al. 2003; Zhou et al. 2008c)
	rs13353224	Additive	8.54E-06	16	63551405	Intergenic
	rs2014572	Additive	7.32E-06	19	62451830	Within 15 kb downstream of AURKC1	Encodes aurora kinase C, a serine/threonine protein kinase, which may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. The gene is expressed in many tissues including brain
	rs10421632	Additive	9.68E-06	19	62456582	Within 25 kb downstream of AURKC1
Inattentive symptom count	rs10227331	Recessive	3.79E-06	7	156987699	Within 40 kb of PTPRN2	Encodes protein tyrosine phosphatase, receptor type, N polypeptide 2, a 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. PTPRN2 shows especially high expression in brain. Lies within linkage region for autism observed in meta-analysis (Trikalinos et al. 2006). In addition, the gene showed association in GWAS of schizophrenia (Sullivan et al. 2008) and of bipolar disorder (Sklar et al. 2008) at P = 10−4
	rs2769967	Recessive	3.63E-06	9	81079178	Intergenic	Close to meta-analytic suggestive linkage region for ADHD (Zhou et al. 2008c)
	rs1471225	Additive	8.09E-06	15	27675688	Within 30 kb downstream of KIAA0574	Encodes protein of unknown function expressed in brain and other tissues. Finding lies within meta-analytic suggestive linkage region for ADHD (Zhou et al. 2008c). The gene is found in CNV regions in 3 studies of autism (Christian et al. 2008; Marshall et al. 2008; Sebat et al. 2007)	Site known for CNVs
	rs7172689	Additive	3.86E-06	15	79320750	Within intron of IL16	Encodes interleukin 16. The protein is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The gene is expressed in many tissues including brain	Also found in GWAS by Neale et al. (2008a)
	rs7172689	Dominant	1.50E-06	15	79320750
	rs4128767	Dominant	1.28E-06	15	79330462

Values indicated in bold are SNPs that appear in the list more than once

^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)

^# These findings were derived using the PBAT screening procedure prior to association testing