Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population.

Attention deficit hyperactivity disorder (ADHD) is a childhood onset neurobehavioral disorder. Several studies worldwide have implicated a possible association between ADHD and transmission of different polymorphisms of the dopamine D4 receptor gene (DRD4) in different ethnic groups. However, this is the first report on the transmission of different polymorphisms of DRD4 in Indian subjects. Association of 5' flanking 120-bp duplication, exon 1 12-bp duplication, and exon 3 48-bp variable numbers of tandem repeats (VNTR) were analyzed in 50 ADHD cases. Haplotype-based haplotype relative risk (HHRR) analysis and transmission disequilibrium test (TDT) were carried out to ascertain the association of these polymorphisms with the disorder. Linkage disequilibria (LD) between the polymorphisms were calculated using EH+ and 2LD programs. Our preliminary data showed lack of association between ADHD and transmission of the 5' flanking 120-bp duplication and exon 1 12-bp duplication. But, the transmissions of 6 and 7 repeat alleles of exon 3 48-bp VNTR showed significant association with ADHD. We have also examined the haplotype frequencies and biased transmission of one haplotype was observed in ADHD probands. LD analysis showed very strong disequilibrium between exon 1 12-bp duplication and exon 3 48-bp VNTR. Strong LD was also observed between the 5' flanking 120-bp duplication and exon 1 12-bp duplication. The observed association between higher repeat alleles of exon 3 48-bp VNTR and Indian ADHD children is consistent with some of the earlier reports.     

Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene

Attention-deficit/hyperactivity disorder (ADHD) is a very common and heterogeneous psychiatric disorder of childhood with marked inattentive, hyperactive, and impulsive symptoms. The DBH gene, the locus that encodes the enzyme dopamine-beta-hydroxylase (DbetaH), seems to be an important candidate gene for association studies, since DbetaH catalyzes the conversion of dopamine to norepinephrine. The aim of this study was to test for association between the DBH gene and ADHD in a sample of 88 Brazilian nuclear families. Haplotype relative risk (HRR) analysis of the DBH TaqI restriction site polymorphism showed a preferential transmission of the TaqI A2 allele in our whole ADHD sample (chi(2)=3.61, one-tailed P=0.03). The significant effect of the A2 allele was stronger when only families with no ADHD parental diagnosis were considered (chi(2)=5.42, one-tailed P=0.01). Our results suggest a contribution of this gene to ADHD susceptibility, partially replicating previous findings that have demonstrated an association between the DBH TaqI A2 allele and ADHD.     

Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios.

The dopamine (DA) system has been implicated in attention deficit hyperactivity disorder (ADHD) based on pharmacologic evidence. Because of an interaction between the serotonin (5-HT) and DA systems, the serotonin transporter gene (SLC6A4) has been considered as a candidate ADHD susceptibility gene. Two common polymorphisms, 5-HTTLPR and the intron 2 VNTR, have been studied for association in ADHD, with both positive (increased frequency of long allele of 5-HTTLPR and decreased frequency of 12 repeats of the intron 2 VNTR) and negative findings. However, there has not been an association study in an East Asian ADHD population. In this study, we examined the genotypes of these two polymorphisms in 126 Korean ADHD families and investigated linkage disequilibrium (LD) between SLC6A4 and ADHD, using the transmission disequilibrium test (TDT) and haplotype analysis. Additionally, association with quantitative measures of inattention, hyperactivity-impulsivity, and overall severity was tested using logistic regression and QTDT analysis. TDT of both polymorphisms and haplotype analysis failed to detect LD. However, after excluding ADHD NOS subtype, TDT revealed nominally significant LD between 5-HTTLPR and ADHD (chi2 = 4.9, P = 0.036). QTDT revealed positive association between 12 repeats of the intron 2 VNTR and attention (P = 0.031), but case-control and TDT logistic regression analyses were negative. These markers have low heterozygosity in the Korean population, which would be expected to reduce the power of association. This result suggests that future studies should include more polymorphic markers and subjects to thoroughly investigate a potential association between SLC6A4 and ADHD in the Korean population.     

A promoter polymorphism (-839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children.

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission and is also the major site of action for methylphenidate which is one of the main drugs used to treat attention deficit hyperactivity disorder (ADHD). Most association studies with ADHD have concentrated on the 3'-untranslated region of the gene (3'-UTR) mainly in a variable number of tandem repeat (VNTR) polymorphism, but these investigations have reported discordant results. In this study, we tested this VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using family-based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D' = 0.56; P = 0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P = 0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P = 0.004). Our results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.     

Association between polymorphisms in the progesterone receptor gene and endometriosis

The progesterone receptor (PR) is a candidate gene for the development of endometriosis, a complex disease with strong hormonal features, common in women of reproductive age. We typed the 306 base pair Alu insertion (AluIns) polymorphism in intron G of PR in 101 individuals, estimated linkage disequilibrium (LD) between five single-nucleotide polymorphisms (SNPs) across the PR locus in 980 Australian triads (endometriosis case and two parents) and used transmission disequilibrium testing (TDT) for association with endometriosis. The five SNPs showed strong pairwise LD, and the AluIns was highly correlated with proximal SNPs rs1042839 (delta2 = 0.877, D9 = 1.00, P < 0.0001) and rs500760 (delta2 = 0.438, D9 = 0.942, P < 0.0001). TDT showed weak evidence of allelic association between endometriosis and rs500760 (P = 0.027) but not in the expected direction. We identified a common susceptibility haplotype GGGCA across the five SNPs (P = 0.0167) in the whole sample, but likelihood ratio testing of haplotype transmission and non-transmission of the AluIns and flanking SNPs showed no significant pattern. Further, analysis of our results pooled with those from two previous studies suggested that neither the T2 allele of the AluIns nor the T1/T2 genotype was associated with endometriosis.     

Lack of association or linkage disequilibrium between schizophrenia and polymorphisms in the 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes: family-based association study.

Genetic factors play a major role in the etiology of schizophrenia and disturbances of serotonergic pathways have been implicated in this disorder. The aim of the present study was to examine genetic association between schizophrenia and polymorphisms in the 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) autoreceptor genes in ninety trios from Portugal. No association or linkage disequilibrium was obtained between schizophrenia and 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT). Concerning 5-HT1Dbeta autoreceptor gene, also negative results was obtained in the analysis of the haplotypes with transmit. Thus, our data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population.     

Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease

Abstract:  In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 ( CELIAC3 ) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles −1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly −1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.     

Possible association of the alpha-2A adrenergic receptor gene (ADRA2A) with symptoms of attention-deficit/hyperactivity disorder.

A dysfunction of the central noradrenergic system has long been suggested to be involved in attention-deficit/hyperactivity disorder (ADHD). Pharmacological evidence from animal studies and clinical practice has identified the alpha-2A adrenergic receptor gene (ADRA2A) as a candidate gene in ADHD. Some findings from Caucasian populations seem to support a role for this gene in ADHD. The current study first examined the association of the ADRA2A MspI and DraI polymorphisms with ADHD in the Han Chinese population, which differs quite substantially from the Caucasian population in the frequencies of alleles at these polymorphisms. No biased transmission of alleles of either polymorphism was observed using transmission disequilibrium test (TDT) analysis in a sample of 268 nuclear families with an ADHD proband; however, haplotype analysis only identified a trend toward over-transmission of the M/C haplotype to probands with the combined subtype of ADHD (chi(2) = 3.233, P = 0.072). The mm genotype of the MspI polymorphism was also marginally related (P = 0.051) to lower ADHD symptom scores in a sample of 559 Chinese children with ADHD, which is inconsistent with data from Caucasian samples. Our results provide weak evidence for a possible role of ADRA2A in ADHD symptom expression.     

Analysis of HLA-DRB and -DQB gene RFLPs in DR7 homozygous cell lines: associations with Dw11, Dw17 and DB1

The DR7-associated Dw specificities, Dw11, Dw17 and DB1 were investigated with regard to DRB- and DQB-gene polymorphism, as revealed by RFLP analysis using the restriction enzyme TaqI. In the 22 DR7 homozygous cell lines investigated, each of these Dw specificities was found to correlate to one specific RFLP defined DR-DQ haplotype. In addition, a clear linkage disequilibrium to a specific HLA-B locus allele for each Dw specificity was noted, indicating that the Dw subtypes of DR7 often are associated with a conserved HLA-B-DR-DQ haplotype. Only one genetically homozygous cell line, PLH, deviated from these correlations. This cell line, notably derived from an individual with a deletion of the 21-hydroxylase B-gene (21-OHB), caries the HLA haplotype Bw47, DR7, DQw2, DB1, but displayed a DRB RFLP otherwise found in association with Dw17.     

Additive effect of three noradrenergic genes (ADRA2A, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects

Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.     

Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+ 1603C --> T) with plasma dopamine beta-hydroxylase activity.

The DBH locus controls plasma dopamine beta-hydroxylase activity (pDbetaH). A 5'-upstream single nucleotide polymorphism (SNP) at DBH (-1021C --> T) explains approximately 45% of the variance in pDbetaH, and a non-synonymous SNP in exon 11 (+ 1603C --> T) an additional 2%. However, that regression result underestimates the effect of + 1603C --> T because of its low minor allele frequency. We estimated the biological effect of + 1603C --> T on pDbetaH by comparing subjects of identical -1021CgammaT genotype, in a diagnostically heterogeneous group of subjects of European origin (N = 367). + 1603C --> T genotype associated with pDbetaH within groups of identical genotype at -1021 C --> T, accounting for 5%-16% of the variance. There was no significant linkage disequilibrium between -1021C --> T and + 1603C --> T (D = 0.0058, D' = 0.4774, d(2) = 0.0011, P > 0.05), confirming the validity of assessing the two polymorphisms independently. These results suggest that altered homospecific activity of the enzyme can contribute to variation in pDbetaH. This conclusion informs how associations between DBH and psychiatric disorders should be approached. (c) 2005 Wiley-Liss, Inc.     

Linkage disequilibrium of MTHFR genotypes 677C/T-1298A/C in the German population and association studies in probands with neural tube defects(NTD).

A number of studies have demonstrated that the common polymorphism 677C-->T in the gene encoding 5, 10-methylenetetrahydrofolate reductase (MTHFR) leads to a thermolabile variant with decreased enzyme activity and to mildly elevated plasma homocysteine. 677TT homozygosity was shown to be more frequent in NTD probands compared with controls in some studies. Recently, another polymorphism, 1298A-->C, in the MTHFR gene was described and combined heterozygosity 677CT/1298AC was suggested to be an additional risk factor for NTD. The present study examines the genotype and haplotype distribution of the two polymorphisms in the German population and evaluates the impact on NTD individuals and their relatives. To determine the haplotype of all individuals tested, we developed an easy-to-perform ARMS-RFLP test. Our data show that the two polymorphisms are in linkage disequilibrium in the general population and in NTD individuals. There was no statistically significant difference in allele and genotype frequency between probands (patients, fetuses) and controls (P > 0.10) and between observed and expected values for mother-child pairs (P > 0.80). Taking into account gender, an increased rate of 677CT heterozygotes was found in affected and unaffected males compared to affected and unaffected females. A family-based association study using a multiallelic transmission disequilibrium test (TDT) also shows that transmission rates do not deviate significantly from equilibrium (P > 0.50). Thus, our data provide no evidence for an association between NTD phenotype and MTHFR 677C/T-1298A/C genotypes and haplotypes.     

Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3.

Family-based linkage disequilibrium (LD) mapping has been suggested as a powerful and practical alternative to linkage analysis. We have performed a genome-wide LD survey of susceptibility loci for schizophrenia in a Japanese population. We first typed 119 schizophrenic pedigrees (357 individuals) using 444 microsatellite markers, and analyzed the data using the pedigree disequilibrium test. This analysis revealed 14 markers demonstrating significant transmission distortion. To corroborate these findings, the statistical methods were changed to the extended transmission disequilibrium test (ETDT), using 80 independent complete trios (schizophrenic proband and both parents), with 68 derived from initial pedigrees and 12 newly recruited trios. ETDT supported two markers for continued association, D11S987 on 11q13.3 (P = 0.00009) and D16S423 on 16p13.3 (P = 0.002). We scrutinized the most significant genomic locus on 11q11-13 by adding 26 new markers for analysis. Results of three-marker haplotype analysis in the region showed evidence of association with schizophrenia (most significant haplotype P = 0.0005, global P = 0.022). Although the present study may have missed other potential genomic intervals because of the sparse mapping density, we hope that it has identified promising anchor points for further studies to identify risk-conferring genes for schizophrenia in the Japanese population. In addition, we provide useful information on genomic LD structures in Japanese populations, which can be used for LD mapping of complex diseases.     

Butyrophilin-like 2 gene is associated with ulcerative colitis in the Japanese under strong linkage disequilibrium with HLA-DRB1*1502

The human leukocyte antigen (HLA) region has been implicated in the pathogenesis of inflammatory bowel disease (IBD), which is classified into Crohn's disease (CD) and ulcerative colitis (UC). Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene was reported. BTNL2 is located in the HLA region and its messenger RNA is expressed most abundantly in the intestine. In this study, we performed a case-control association study of BTNL2 in the Japanese patients with IBD and performed linkage disequilibrium (LD) analysis between BTNL2 and HLA-DRB1. We analyzed eight polymorphisms selected after direct sequencing and found that none of the polymorphisms were associated with the Japanese CD cohort. In contrast, five polymorphisms were significantly associated with UC, especially three single nucleotide polymorphisms (BTNL2_19, BTNL2_22 and BTNL2_23) were associated as a haplotype. The most frequent haplotype (GGC haplotype) was a low-risk haplotype (P= 0.000052), whereas the other TCT haplotype was a high-risk haplotype (P= 0.0000085). Among the eight polymorphisms, the strongest association with UC was found in BTNL2_19 (OR = 1.92, P= 0.0000035). As expected, the BTNL2_19-T allele showed strong LD with DRB1*1502 (D'= 0.92). When BTNL2_19 was tested as conditional on the DRB1*1502 carrier status, the significant association disappeared, suggesting that the association was because of its strong LD with DRB1*1502. We conclude that BTNL2 does not contribute to the susceptibility to Japanese CD but is associated with Japanese UC because of the strong LD with HLA-DRB1*1502. The strong LD between BTNL2 and HLA-DRB1 raises another issue about the potential role of BTNL2 in other diseases associated with HLA-DRB1.     

Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Serotonin is an endogenous neurotransmitter that regulates aggressive and impulsive behavior and may be involved in the development of attention deficit hyperactivity disorder (ADHD). 5-HT1B knockout mice display hyperactivity, increased exploratory activity and aggression, reduced anxiety, increased vulnerability to cocaine self-administration, and elevated alcohol consumption. Many of these same behaviors are seen in patients with ADHD. Prior studies reported excess transmission of the 861G allele of 5-HT1B to ADHD offspring. We used the transmission disequilibrium test (TDT) and haplotype analysis to investigate the A-161T and G861C polymorphisms in the 5-HT1B receptor gene in ADHD trios from the Chinese Han population. We found no association with ADHD but did find a tendency for excess transmission of the 861G allele (chi(2) = 3.766, P = 0.052) and the G/A haplotype (chi(2) = 2.925, df = 1, P = 0.087), and under-transmission of C/A haplotype (chi(2) = 3.707, df = 1, P = 0.054) to offspring with inattentive ADHD.     

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114-117, 2000.     

Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese

A linkage disequilibrium (LD) between the alcohol-dehydrogenase 1B (ADH1B) and alcohol-dehydrogenase 1C (ADH1C) polymorphisms adds complexity to differentiating the significance of these two genetic polymorphisms on drinking behavior and alcoholism. We have recently shown the importance of the ADH1B polymorphism on habitual drinking in the Japanese population; however, the issue regarding the LD between the ADH1B and ADH1C polymorphisms remains to be clarified. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese individuals. Drinking behavior was examined with regard to haplotypes of the ADH1B and ADH1C polymorphisms. Strength of association was assessed by sex and aldehyde-dehydrogenase 2 (ALDH2) adjusted odds ratios (OR) and their 95% confidence intervals (CIs) for the haplotype of the ADH1B and ADH1C polymorphisms. The ORs for habitual drinking were significant for ADH1B*2(rapid)-ADH1C*2(slow) (OR = 1.03; 95% CI: 1.01-1.05), ADH1B*1(slow)-ADH1C*1(rapid) (OR = 1.15; 95% CI: 1.14-1.16), and ADH1B*1(slow)-ADH1C*2(slow) (OR = 1.31; 95% CI: 1.29-1.32) compared with ADH1B*2(rapid)-ADH1C*1(rapid). This trend was evident among males. Similarly, a significantly increased risk of heavy drinking was observed for each haplotype compared with ADH1B*2(rapid)-ADH1C*1(rapid). In conclusion, this study showed a significant impact of the ADH1C polymorphism on habitual drinking, regardless of the ADH1B/ALDH2 polymorphisms.     

Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects

Attention-deficit/hyperactivity disorder (ADHD) is an important public health problem. Although serotonin is believed to be an important neurotransmitter in the etiology of this disorder, it remains unclear which specific 5-HT receptors are involved in regulating the symptoms of ADHD. Previous studies have provided favorable evidence for the association of ADHD with both the serotonin transporter gene and serotonin 1B receptor gene. To further investigate the role of other genes of the serotonergic pathway in ADHD, the current study examined variants of the serotonin 4 receptor gene in a relatively large sample of ADHD nuclear families. The T allele of the 83097 C>T polymorphism of HTR4 showed a tendency of preferential transmission to probands with ADHD (chi(2)=2.699, P=0.100). When haplotype TDT analysis of HTR4 was performed, we further found that the C/G haplotype of the 83097 C>T and 83198 A>G polymorphisms (chi(2)=8.783, P=0.003) and the C/G/C haplotype of these and the -36 C>T polymorphism (chi(2)=5.762, P=0.016) were under-transmitted to probands with ADHD. These results suggest that the HTR4 gene may play a role in the genetic predisposition to ADHD.     

The transmission disequilibrium analysis between neuronal nicotinic acetylcholine receptor alpha 7 subunit gene polymorphisms and schizophrenia]

OBJECTIVE: To investigate the association between neuronal nicotinic acetylcholine receptor alpha 7 subunit (CHRNA7) gene and schizophrenia. METHODS: The three polymorphisms rs2337980, rs1909884, rs883473 in CHRNA7 gene were detected based on PCR and polyacrylamide gel microarray in 129 schizophrenic trios. The results of genotyping were analyzed by haplotype relative risk analysis based on haplotype(HHRR), transmission disequilibrium test(TDT) and hyplotype analysis. RESULTS: (1)The HHRR analysis suggested that there was significant differences in rs2337980 allele frequencies between schizophrenia group and dummy control group(P= 0.017); (2)In TDT test, there may be transmission disequilibrium between rs2337980 and schizophrenia, the heterozygous parents excessively transferred the C allele to patients (P= 0.021); (3)The haplotype between rs2337980 and rs1909884 as well as the hyplotype among rs2337980, rs1909884 and rs883473 may have significant association with schizophrenia (global P= 0.034; global P= 0.027), the T-C and T-C-T hyplotype may have transmission disequilibrium with schizophrenia. CONCLUSION: There may be association between CHRNA7 gene polymorphisms and schizophrenia, the variant allele T in rs2337980 may have a protective effect to schizophrenia.     

Linkage disequilibrium analysis of the dopamine beta-hydroxylase gene in persistent attention deficit hyperactivity disorder

Numerous family, twin and adoption studies have reported a strong genetic component for attention deficit hyperactivity disorder (ADHD). In addition, an extensive amount of literature has implicated abnormalities of the dopaminergic system. In view of this evidence, genes that influence dopaminergic transmission have become prime candidates for molecular genetic investigations of ADHD. There are currently three studies (Daly et al., 1999; Roman et al., 2002; Wigg et al., 2002) that have found an association between the dopamine beta-hydroxylase gene (DBH) TaqI 2 allele and childhood ADHD. As such, we tested for association of the DBH TaqI 2 allele in two independent samples of patients with the persistent variant of ADHD. These consisted of 97 nuclear families, and 112 adult cases with controls carefully matched according to gender, age and ethnicity. Transmission Disequilibrium Test analysis revealed weak over-transmission of the 2 allele (35 transmissions versus 27 non-transmissions; chi2 = 1.03, 1 degree of freedom, P=0.31). The case-control sample did not support previous findings since the 2 allele was more frequent in our control sample (137 versus 116; chi2 = 3.63, 1 degree of freedom, P=0.057). Taken together, these results do not provide support for a role of the DBH TaqI marker in our persistent ADHD samples.