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Results for “Association analysis”

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PubMed2006

Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.

OBJECTIVE: To determine whether SNPs within the dopamine transporter gene (DAT) are associated with quantitative phenotypes generated from drug frequency variables in an ADHD sample. METHOD: 35 SNPs were genotyped in and around DAT. We developed a quantitative phenotype at each SNP by weighting the drug frequency variables. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, a screening procedure was used to select and test the SNPs with the greatest power to detect an association in DAT. RESULTS: No SNPs in DAT were associated with the quantitative phenotypes generated from the drug frequency variables after the multiple comparisons adjustment; however, some SNPs achieved nominal significance. A sliding window of analysis of 3 SNPs also resulted in only nominal associations. CONCLUSIONS: SNPs in DAT do not appear to be associated with the phenotypes generated from drug frequency variables among individuals with ADHD.

Adolescent↗

PubMed2004

Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes.

Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model make LCK a premier candidate for a susceptibility gene. Resequencing of LCK in 32 individuals detected seven single nucleotide polymorphisms (SNPs) with allele frequencies >3%, including four common SNPs previously reported. These and six other SNPs from dbSNP were genotyped in a two-stage strategy using 2,430 families and were all shown not to be significantly associated with type 1 diabetes. We conclude that a major role for the common LCK polymorphisms in type 1 diabetes is unlikely. However, we cannot rule out the possibility of there being a causal variant outside the exonic, intronic, and untranslated regions studied.

Adult↗

PubMed2000

Association analysis of two tyrosine hydroxylase gene polymorphisms in normotensive offspring from hypertensive families.

OBJECTIVE: We have studied possible association between predisposition to essential hypertension, plasma noradrenaline level and two polymorphisms of the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. DESIGN AND METHODS: One hundred and one normotensive sons from normotensive parents (SN) and 107 normotensive sons of hypertensive families (SH) were studied. Tetranucleotide TCAT repeat and Va181Met polymorphisms of the TH gene were determined by polymerase chain reaction (PCR) technique. RESULTS: SH had higher systolic BP and plasma noradrenaline concentration than the SN group. No significant difference was found between the allele and genotype frequencies in the SH and SN groups for both polymorphisms. The two polymorphisms were in tight linkage disequilibrium. The CD genotype of the microsatellite marker was associated with increased plasma noradrenaline concentration in both groups. Genotypes AB, AE and BB of the TCAT repeat polymorphism and genotypes VM and MM of the Va181Met polymorphism exhibited the greatest difference in plasma noradrenaline concentration between the SH and SN groups. CONCLUSION: The studied TH polymorphisms do not appear to be associated with family history of essential hypertension. Nevertheless, some genotypes of TH might be related to disturbance of plasma noradrenaline concentration.

Adult↗

PubMed2004

Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease.

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD. METHODS: In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness. RESULTS: A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E. CONCLUSIONS: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

Aged↗

PubMed2005

Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study.

BACKGROUND: Reproducibility of results is important for the validity of genetic association studies. Recently, 3 functional polymorphisms, G(-930)A in CYBA, T481S in CLCNKB, and E65K in KCNMB1, were reported to be associated with blood pressure (BP) status and the aim of this study was to confirm those findings using a large cohort representing the general Japanese population. METHODS AND RESULTS: The study population consisted of 3,652 subjects recruited from the Suita study as representative of the general population in Japan. The genotypes of the 3 polymorphisms were determined by the TaqMan method. Logistic analysis indicated that the CYBA/G(-930)A polymorphism was associated with hypertension in male subjects. In the male population, the odds ratio of the GG genotype over GA + AA was 1.27 (95% confidence interval 1.01-1.57, p=0.034). Moreover, residuals of systolic and diastolic BP values were significantly higher in subjects with the GG genotype than in those with the GA or AA genotype (p=0.0007). However, such significant effects of the genotype on BP status were not observed in the female population. The significance of the CLCNKB/T481S and KCNMB1/E65K polymorphisms were not replicated in the present study. CONCLUSION: The significance of the G(-930)A polymorphism of CYBA was confirmed in the present study with adequate statistical power, which strengthens the hypothesis that this polymorphism is important in the pathogenesis of hypertension and confers susceptibility.

Aged↗

PubMed2004

Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia.

OBJECTIVE: Recent studies have revealed positive associations between tardive dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP) subfamilies that are involved in pharmacokinetic process of antipsychotic drugs. In the present study, we analyzed the relationship between TD and two polymorphisms of the CYP1A2 gene, 734C/A and -2964G/A, in a sample of Japanese patients with schizophrenia. METHODS: We studied 199 Japanese patients with schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD. Two polymorphisms of the CYP1A2 gene, 734C/A and -2964 G/A were genotyped by means of polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Neither the 734C/A nor the -2964G/A polymorphism was associated with TD [734C/A genotype: chi2=0.02, degrees of freedom (df)=2, P=1.00; allele: chi2=0.02, df=1, P=0.89; -2964G/A genotype: chi2=0.21, df=2, P=0.90; allele: chi2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was associated with TD (chi2=0.24, df=3, P=0.97). Furthermore, in both the subgroup of smokers and the subgroup of patients receiving high-dosage antipsychotics (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the -2964G/A polymorphism was associated with TD. CONCLUSIONS: We did not find significant associations between the 734C/A and -2964G/A polymorphisms of CYP1A2 gene and TD in Japanese patients with schizophrenia. Our results suggest that these CYP1A2 gene polymorphisms may not contribute to TD susceptibility.

Adult↗

PubMed2003

Family-based association analysis with tightly linked markers.

Refining genomic regions which have been identified by linkage analysis to contain a disease susceptibility locus has proven to be a challenging task. Detecting association between the disease and a genetic marker can significantly narrow down the candidate region. Since an adequate sample of families is already available from the genome scan, family-based association tests may be used to search for association. The use of haplotypes consisting of tightly linked markers can be more powerful for detecting association than the use of individual markers. An extension of the transmission/disequilibrium test to allow the simultaneous analysis of more than one marker locus is complicated by ambiguity of phase in some families of the sample. The present paper shows that a recently proposed method for the analysis of nuclear families with a single affected child can be viewed as a special application of a more general principle. This observation justifies several modifications, potentially increasing the power, as well as an extension of the method to allow the analysis of general nuclear families. Finally, the problem of missing parental genotypes is discussed.

Chromosome Mapping↗

PubMed1993

Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population.

An association study of the insertion/deletion (I/D) polymorphism located in intron 16 of the ACE gene with essential hypertension in the Japanese population was performed. The 287 bp I/D polymorphism was detected by polymerase chain reaction. Derived allele frequencies for insertion and deletion were not significantly different between 133 hypertensive and 104 normotensive subjects. A significant relationship between I/D polymorphism and plasma ACE activity was observed in the normotensive group, but not in hypertensives. These results suggest that I/D polymorphism of the gene is not implicated in Japanese hypertensive subjects, and that studies involving various ethnic groups are important.

Adult↗

PubMed2006

[Association analysis of the essential hypertension susceptibility genes in adolescents: Kangwha study].

OBJECTIVES: In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T-344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T-47C, T164I), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. METHODS: The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. RESULTS: In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p = 0.0403), AGT (M235T) (p = 0.0002), and REN (G2646A) (p = 0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. CONCLUSIONS: This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

Adolescent↗

PubMed2005

Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy.

PURPOSE: Linkage disequilibrium mapping revealed allelic and haplotypic associations between single-nucleotide polymorphisms (SNPs) of the gene encoding the malic enzyme 2 (ME2) and adolescent-onset idiopathic generalized epilepsy (IGE). Homozygote carriers of the associated ME2 haplotype had a sixfold higher risk of IGE compared with any other genotype. The present population-based association study tested whether genetic variation of the ME2 gene confers susceptibility to common IGE syndromes in the German population. METHODS: The study included 666 German healthy control subjects and 660 German IGE patients (IGE group), of which 416 patients had an age at onset in adolescence (IGEado group). Genotyping was performed for six SNPs and one dinucleotide repeat polymorphism, all located in the ME2 region. RESULTS: Neither allele nor genotype frequencies of any ME2 polymorphism differed significantly between the controls and the IGE groups (p > 0.22). No hint of an association of the putative risk-conferring haplotype was seen, when present homozygously, in both IGE groups compared with controls (p > 0.18). CONCLUSIONS: These results do not support previous evidence that genetic variation of the ME2 gene predisposes to common IGE syndromes. Thus if a recessively inherited ME2 mutation is present, then the size of the epileptogenic effect might be too small or not frequent enough to detect it in the present IGE sample.

Age of Onset↗

PubMed2005

Association analysis of the variant in the regulatory subunit of phosphoinositide 3-kinase (p85alpha) with Type 2 diabetes mellitus and hypertension in the Chinese Han population.

AIMS: To determine whether variants in the gene for the regulatory subunit of phosphoinositide 3-kinase (p85alpha) are associated with Type 2 diabetes mellitus (Type 2 DM) and hypertension in a Chinese population. METHODS: We performed a case-control study genotyping the Met326Ile and IVS4+82A>G polymorphisms in 494 patients with Type 2 DM and hypertension and 557 normal controls from the north of China. Individual genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The IVS4+82A>G polymorphism was further confirmed by direct sequencing in 20 randomly selected cases. RESULTS: The IVS4+82A>G polymorphism that is common in Caucasians was not detected in our population. Frequencies of genotypes and alleles of Met326Ile polymorphism were not significantly different between cases and controls in whole samples by univariate analysis. Logistic regression analysis demonstrated that Ile326Ile genotype was associated with a 2.085-fold (95% CI, 1.043-4.168, P = 0.0377) relative risk of diabetes and hypertension. After stratification by obesity, the frequency of Ile326Ile genotype in cases was higher than that in controls (18/304 vs. 13/510, P = 0.015) among non-obese individuals (BMI < 28 kg/m2). We did not find that this missense mutation was associated with blood pressure, glucose and blood lipids in the control group. CONCLUSION: Our data indicate that the Met326Ile variation in the gene encoding the p85alpha protein might contribute to the increased risk of Type 2 DM and hypertension in Chinese.

Aged↗

PubMed2000

Association analysis between mood disorder and monoamine oxidase gene.

To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000.

Alleles↗

PubMedDate not supplied

The VATER association: analysis of forty six cases without karyotyping.

Forty-six patients with two or more features of the VATER association admitted to the Mackay Memorial Hospital from May, 1983 to Mar, 1992 were retrospectively enrolled in this study. We compared the incidence of major features with that reported in the literature. Imperforate anus, congenital heart disease, and renal anomalies were the three most common major features in our study. Thirteen patients died. Heart failure was the major cause of mortality. We noted many patients associated minor features, and among them there was a relatively high ratio of cleft lip, cleft palate, and hypospadius. The overall outcome and development were good among the survivals. We suggest that children who have any congenital anomaly included in the VATER association should get a careful examination and evaluation of their heart, genitourinary tract, limbs and vertebrae. Early correction if possible is indicated in such patients.

Abnormalities, Multiple↗

PubMed2003

[Association analysis between attention-deficit hyperactivity disorder and Val158Met polymorphism of catechol-O-methyltransferase gene].

OBJECTIVE: To investigate the association between attention-deficit hyperactivity disorder (ADHD) in Han Chinese children and Val158Met polymorphism of catechol-O-methyltransferase (COMT) gene caused by the missense mutation of G158A in exon 4. METHODS: By using polymerase chain reaction-restriction fragment length polymorphisms the Val158Met polymorphism of COMT gene was tested in 117 children with the diagnosis of ADHD as defined by DSM-IV and in 105 healthy controls living in Shanghai. RESULTS: The frequencies of A allele were 25.21% and 23.81% in the ADHD group and the health controls respectively, which showed no significant difference between the two groups (Chi2=0.5197, P>0.05). There was also no significant difference in the distribution of all genotypes of COMT gene between the ADHD patients and the controls (P>0.05). CONCLUSION: It was suggested that for the Han Chinese children with ADHD in this study, there was no association between ADHD and Val158Met polymorphism of COMT gene.

Adolescent↗

PubMed2006

Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients.

Mutations in the autoimmune regulator (AIRE) gene cause a recessive Mendelian disorder autoimmune polyendocrinopathy syndrome type 1 (APS-1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). APS-1 patients develop multiorgan autoimmune diseases including type 1 diabetes (prevalence 12%). The AIRE protein controls the central tolerance induction in the thymus by regulating the expression levels of tissue-specific peripheral antigens, such as insulin. We hypothesized that the insulin gene (INS) polymorphisms together with the AIRE variations may predispose individuals to diabetes. The role of the AIRE gene was tested both independently and on the condition of the INS risk genotype in the Finnish type 1 diabetes sample. A total of 733 type 1 diabetic cases and 735 age- and sex-matched healthy controls were used in the analysis. Five common single nucleotide polymorphisms (SNPs) in the AIRE gene were selected from the public database (dbSNP). The -23HphI polymorphism was used as a surrogate marker for the INS gene promoter repeat. The five genotyped SNPs in the AIRE gene showed no evidence of association with type 1 diabetes. As expected, the INS gene polymorphism -23HphI was significantly associated with susceptibility to type 1 diabetes (P=6.8 x 10(-12), chi(2) test). When the subclass of patients carrying the homozygote genotype of the INS gene was used in the analysis, the AIRE polymorphisms showed no association with the disease. In conclusion, the AIRE gene does not seem to contribute to disease susceptibility in Finnish type 1 diabetic patients, whereas the insulin gene represents a notable risk factor for disease in this population.

Adult↗

PubMed2006

Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19.

Evidence from four independent linkage studies and two meta-analyses of genome-wide data support the existence of a locus conferring susceptibility to inflammatory bowel diseases (IBD) in chromosomal region 19p. Identification of a susceptibility allele in this approximately 28.5 Mb region with over 600 genes is a formidable task. To tackle this problem, we undertook two approaches: (1) haplotype-based candidate-gene screen, and (2) evaluation of previously reported associations. For the former, we selected genes with potential implication in IBD pathogenesis based on published functional and expression data, typed SNPs, constructed haplotypes, screened for association in 180 IBD trios, and followed up preliminary associations in 343 IBD patients and 207 control individuals. Overall, we analyzed 465 SNPs, and 260 haplotypes distributed across 56 candidate genes. We found suggestive evidence of association (nominal P<0.01) with four genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to confirm these preliminary observations at follow-up. In the second approach, we typed four nonsynonymous polymorphisms in genes C3 (R102G and L314P) and ICAM1 (G241R and K469E) in four independent cohorts totaling 2178 IBD cases. We evaluated these data together with previously published reports for three of these variants (C3-Gly102, ICAM1-Arg241, and ICAM1-Glu469), in a meta-analysis. Our pooled meta-analysis provides compelling evidence against association of these variants with disease. Overall, we performed the most comprehensive candidate-gene association study for IBD to date. The information hereby generated constitutes a valuable resource to investigate other common genetic immune diseases, such as celiac disease.

Alleles↗

PubMed1999

Association analysis of the 5-HT6 receptor polymorphism C267T in Alzheimer's disease.

Serotonergic dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). This association study explores whether the serotonin 6 receptor (5-HT6) polymorphism (C267T) is a susceptibility factor for AD. Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and the normal controls (P = 0.006; and P = 0.023, respectively). These findings indicate that the 267C allele of the 5-HT6 gene is a risk factor for AD.

Aged↗

PubMed2000

Association analysis between bilateral convergent strabismus with exophthalmus and milk production traits in dairy cattle.

Bilateral convergent strabismus with exophthalmus (BCSE) is characterized in cattle by a symmetrical antero-medial rotation and protrusion of the eyeballs. This eye defect is caused by an inherited, centrally insufficient function of the eye muscles recti laterales and retractores. In German Brown cattle a monogenic, autosomal dominant inheritance proved to be most probable in complex segregation analysis. In our study running between October 1993 and May 1995 a total of 200 affected German Brown cows was studied. The investigation of the association between milk production traits and BCSE was based on 10,960 German Brown cows. The analysis revealed no significant differences between affected and non-affected cows, nor between cow families with and without affected members. There was no indication of an association between milk production traits and occurrence of BCSE within cow families. Linkage or pleiotropy of the BCSE locus with quantitative trait loci for milk production traits may be rather unlikely.

Animals↗