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Results for “Association analysis”

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PubMed2025

Association Analysis of the Circulating Proteome With Sarcopenia-Related Traits Reveals Potential Drug Targets for Sarcopenia.

BACKGROUND: Sarcopenia severely affects the physical health of the elderly. Currently, there is no specific drug available for sarcopenia. This study aims to identify pathogenic proteins and druggable targets for sarcopenia through Mendelian randomization (MR)-based analytical framework. METHODS: A sequential stepwise screening method that includes two-sample MR, Steiger filtering test and colocalization (MRSC) was applied to identify causal proteins associated with sarcopenia-related traits. In the MR analyses, 4372 circulating proteins with valid instrumental variables (IVs) from eight proteomic genome-wide association studies were utilized as exposures, and nine sarcopenia-related traits were utilized as outcomes. IVs were classified into cis-protein quantitative trait loci (pQTLs) and trans-pQTLs based on their positions. We conducted cis-only MRSC analyses and cis + trans MRSC analyses using cis-pQTLs and cis + trans pQTLs as IVs, respectively. Post-MRSC analyses were conducted on the prioritized findings of MRSC, including annotation of protein-altering variants (PAVs), assessment of overlap between pQTLs and expression quantitative trait loci (eQTLs), protein-protein interaction (PPI) analysis, pathway enrichment analysis and annotation of drug targets. Utilizing data from the UK Biobank, we performed an observational study to explore the associations between baseline circulating protein levels and the longitudinal changes in nine sarcopenia-related traits. RESULTS: A total of 181 causal associations for 65 proteins were prioritized by the cis-only MRSC analyses and 227 associations for 91 proteins were prioritized by the cis + trans MRSC analyses. Among the prioritized proteins, the majority of them employed non-PAVs as IVs and most of their cis-pQTLs overlapped with corresponding eQTLs and exhibited consistent directionality, with only one trans-pQTL overlapping with an eQTL. The PPI network of cis-only MRSC-prioritized proteins (p = 4.04 × 10-4) and cis + trans MRSC-prioritized proteins (p = 8.76 × 10-5) showed significantly more interactions than expected. Reactome, KEGG and GO pathway enrichment analyses for cis-only MRSC-prioritized proteins identified 52, 12 and 79 enriched pathways, respectively (adjusted p < 0.05). For proteins identified by cis + trans MRSC analyses, only 15 pathways were enriched through the GO pathway enrichment analyses. In the observational study, 197 circulating proteins were identified to be associated with one or more sarcopenia-related traits (p < 0.05/2923). Among them, the significant associations of CTSB (negative association) and ASGR1 (positive association) with sarcopenia-related traits were observed to have consistent directional associations in both MR-based studies and observational studies. Drug target annotations suggested that 52 MRSC-prioritized proteins and 145 biomarkers are drug targets or druggable. CONCLUSIONS: This study identified 89 potential pathogenic proteins and 197 candidate biomarkers for sarcopenia, providing valuable clues for the development of therapeutic drugs for sarcopenia.

Humans↗

PubMed2005

Association analysis of interleukin 5 receptor alpha subunit (IL5RA) polymorphisms and asthma.

The alpha subunit of interleukin 5 receptor (IL5RA) on chromosome 3p26-p24 is known to regulate the development and function of eosinophils. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we investigated the genetic polymorphisms in IL5RA to evaluate the gene as a potential candidate for a host genetic study of asthma. By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within exons and flanking regions including a 1.5-kb promoter region of IL5RA; 10 common polymorphic sites were selected for genotyping in our asthma cohort (n = 587). Two haplotype blocks were identified in a Korean population. Statistical analysis revealed that one promoter SNP, c.-5993A > G, and one ins/del polymorphism in intron 3, c.-480_482insdelGTT, showed significant association with the risk of asthma development. The genetic effects of c.-5993A>G and c.-480_482insdelGTT on asthma were more apparent among atopic subjects. Our findings suggest that polymorphisms in IL5RA might be among the genetic risk factors for asthma development, especially in atopic populations. IL5RA variant/haplotype information identified in this study will provide valuable information for strategies for the control of asthma.

Adolescent↗

PubMed2004

Genetic aberrations in prostate carcinoma detected by comparative genomic hybridization and microsatellite analysis: association with progression and angiogenesis.

BACKGROUND: In spite of increasing knowledge about the tumor biology of prostate cancer (PC), molecular events involved in tumor progression are not well characterized. There is evidence that a number of genetic alterations play a role in tumor progression and in addition, angiogenesis also contributes. In this study, comparative genomic hybridization (CGH), a sensitive method for detecting regional DNA copy number abnormalities, and microsatellite analysis was used to identify frequent genome changes in PC. Correlation of these data with microvessel density (MVD) and clinical follow-up data was performed to determine genetic alterations that are associated with angiogenesis and subsequent tumor progression. METHODS: Fifty-seven paraffin embedded radical prostatectomy (RP) specimens were microdissected. DNA from the microdissected PC tissue was amplified by degenerate oligonucleoitide primed (DOP)-polymerase chain reaction (PCR), and CGH was performed on the PCR product. Quantitative analyses of the CGH profiles were performed using a t-statistic. Additionally, a microsatellite analysis of chromosome 13q was performed on a subgroup of 31 of the tumors. Using a polyclonal antibody against factor VIII, MVD was determined for all RP specimens. The results of CGH and microsatellite analysis were correlated with the clinical data of the patients and with MVD. RESULTS: Forty-two of the tumors (75%) showed one or more gains while 39 (70%) showed one or more losses per tumor. The most frequent DNA copy number gains were on chromosome 3, 4, 7, 8, 10, 11, 12, 13, and X. The most frequent losses were on chromosomes 2, 5, 6, 8, 10, 13, 15, and 16. Cancer recurrence occurred in 15 patients. The total number of DNA copy number losses was significantly higher in patients with this progression (86%) than without (52%) (P < 0.001). There was no significant difference in the number of gains in patients with or without progression. Contingency table analysis showed a significant correlation between progression and losses in regions of chromosomes 6q and 13q and a gain of chromosome 7q. In multivariate analysis, only loss of chromosome 6 was independently prognostic. The gains that correlated most closely with MVD > 35 were on chromosomes 2q, 7q, and Xq, while the losses most closely associated with MVD > 35 were on chromosomes 8q, 10q, and 13q. However, only the association between loss of chromosome 13q and MVD > 35 was statistically significant. Microsatellite analysis revealed a statistically significant correlation between MVD and instability of locus 171. CONCLUSIONS: This study indicates that the frequency of genetic alterations in PC as detected by CGH correlates with clinical outcome, and that losses of DNA from chromosomes 6q and 13q are important events that correlate with tumor progression, with loss of 13q, especially instability of locus 171, also associated with angiogenesis.

Chromosome Aberrations↗

PubMed2004

Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients.

The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years. However, the existence of inconsistent reports makes the role of the DRD3 ser9gly polymorphism in TD development questionable. In rodent studies, the DRD3 expression could be controlled by the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family. In this study, we examined the association between the DRD3 ser9gly and BDNF val66met genetic polymorphisms and TD occurrence in 216 schizophrenic patients (TD/non-TD = 102/114). In addition, we also studied the effects of the DRD3 ser9gly and BDNF val66met genotypes and their gene-gene interaction on the clinical expression of TD in these TD patients. We found that the TD patients who were heterozygous for the BDNF genotypes had significantly higher abnormal involuntary movement scale (AIMS) orofacial scores (corrected p = 0.021, Bonferroni correction), and a trend of higher AIMS total and limb-trunk scores than the combined homozygous analogs. The correlation between the DRD3 ser9gly genotypes and its interaction with the BDNF val66met polymorphism, and the three classes of AIMS scores were not statistically significant. Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence. We concluded that the BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after TD has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary.

Adolescent↗

PubMed2006

Association analysis of the PTPN22 gene in childhood-onset systemic lupus erythematosus in Mexican population.

Several studies have identified a functional single nucleotide polymorphism 1858C/T in the PTPN22 gene to be associated with several autoimmune diseases. Association studies of this polymorphism with familial and sporadic systemic lupus erythematosus (SLE) have shown some discrepancies. To our knowledge, this is the first study that includes only pediatric-onset SLE patients. We performed a case-control association study in 250 unrelated Mexican patients with childhood-onset SLE consisting of 228 cases with sporadic SLE and 22 cases with familial SLE and 355 healthy controls. We observed a statistically significant difference in the frequency of the PTPN22 1858T allele between SLE patients (3.4%) and healthy controls (1.1%) (P=0.0062, odds ratio (OR) 3.09 (95% confidence interval 1.32-7.21)). The association was also observed when only sporadic cases were analyzed (OR=3.19). Our results support the association of the PTPN22 1858T allele with sporadic childhood-onset SLE in Mexican population.

Adolescent↗

PubMed2002

Genetic association analysis using microsatellite markers in atopic dermatitis.

Atopic dermatitis (AD) is presumed to be influenced by genetic and environmental factors. In this study, 54 patients with AD were examined for disease association by the use of 12 microsatellite markers. Several significant associations were recognized in the alleles on chromosome 5, 7 and 11. AD genes were mapped near the FC epsilon RI beta gene (around D11S1314 locus) on chromosome 11, the IL4 gene cluster on chromosome 5 and the TCR gamma gene on chromosome 7. This distribution in close proximity to candidate loci for AD is very similar to that of atopic genes, therefore implying that an atopic trait is genetically responsible for the development of AD.

Adult↗

PubMed2005

Genetic association analysis of chronic mountain sickness in an Andean high-altitude population.

BACKGROUND AND OBJECTIVES: Millions of people live above an altitude of 2,500 m and are at risk of chronic mountain sickness (CMS), a disorder of excessive red cell and hemoglobin production. Preferential ethnic backgrounds, familial character, and heritability studies have suggested that genetic factors make a major contribution to the pathogenesis of CMS, thus our goals were to exploit a probable founder or population admixture effect in the Andean population to determine the genetic determinants of the extreme erythropoietic responses and CMS. DESIGN AND METHODS: The association of functional candidate genes with severe polycythemia was studied in Andean subjects from Cerro de Pasco, Peru (altitude 4,438 m). We used microsatellites linked to candidate genes known to be involved in hypoxia sensing and erythropoiesis: erythropoietin, erythropoietin-receptor, hypoxia-inducible factor-1a, von Hippel-Lindau, prolyl hydroxylase domain containing 1, 2, 3, and phosphatase and tensin homolog deleted on chromosome ten. Analysis of co-variance (ANCOVA) was used to test the effect of genotypes on hemoglobin values. RESULTS: Case-control comparisons revealed no significant difference in genotype and allele frequencies at any marker. Initial analysis, with age as a covariate, showed a possible association between PHD3 (marker D14S1049) and severe polycythemia (p=0.05). After the inclusion of alternative co-variates and after adjusting for multiple comparisons, no p values could be considered statistically significant. INTERPRETATION AND CONCLUSIONS: Our study does not find evidence of associations between the polymorphisms linked to the candidate genes and severe polycythemia; this does not, however, exclude that variations in these genes contribute to polycythemia and possibly CMS.

Adult↗

PubMed2005

Association analysis of transcripts from the bipolar susceptibility locus on chromosome 4q35, exclusion of a pathogenic role for eight positional candidate genes.

Bipolar affective disorder is a major psychiatric illness with a population prevalence of up to 1.6%. The disorder is genetically complex. To date, no specific gene or DNA sequence variation that predisposes to the disorder has been described, however several susceptibility loci have been proposed through genetic linkage analysis. We previously identified one such susceptibility locus on chromosome 4q35, and refined the interval harboring this susceptibility gene to a size that is amenable to positional cloning. Several independent studies have now been described that support the presence of a susceptibility gene at this locus. In order to identify candidate genes for testing association with bipolar disorder, we previously established a comprehensive transcript map that encompasses the chromosome 4q35 susceptibility locus implicated in our linkage analysis. In this study, we have selected full-length genes from the transcript map and determined the genomic structure of each gene. We identified informative, intragenic single nucleotide polymorphisms (SNPs) by screening all exons and flanking intron sequences in affected individuals from seven bipolar pedigrees that we previously reported as showing evidence for linkage to chromosome 4q35. Analysis of these SNPs was then extended to our unrelated bipolar case-control cohort to test for association with the disorder. Our data suggests that all genes analyzed can be excluded from direct involvement in the disorder. We have therefore, excluded approximately half the genes within the chromosome 4q35 candidate interval from playing a direct pathogenic role in bipolar disorder.

Alleles↗

PubMed2004

Association analysis of the -308G>A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia.

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (-308G > A) of the gene encoding tumor necrosis factor alpha (TNF-alpha), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the -308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the -308G > A polymorphism of the TNF-alpha gene.

Adenine↗

PubMed2004

Association analysis of dopamine D2-like receptor genes and methamphetamine abuse.

OBJECTIVES: Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. This study employs an association approach to examine the genetic underpinning of methamphetamine (MAMP) use and MAMP-induced psychosis. METHODS: A total of 416 MAMP abusers from a hospital and a detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis. RESULTS: None of the three markers we studied were associated with predisposition to psychosis among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the seven-repeat allele of DRD4 than normal controls. CONCLUSIONS: Chance fluctuations in the frequency of rare alleles and ascertainment differences in the case and control samples cannot be ruled out. Therefore, further studies of the seven-repeat allele in MAMP abusers and controls should be performed before an association can be established.

Female↗

PubMed2000

Evaluation of fine mapping strategies for a multifactorial disease locus: systematic linkage and association analysis of IDDM1 in the HLA region on chromosome 6p21.

The positional cloning of multifactorial disease genes is a major challenge in human genetics. We have therefore empirically tested the utility of the available polymorphic microsatellite map to locate the already identified type 1 diabetes locus IDDM1 (sibling risk/population prevalence ratio lambda(s)= 2.7) within a 14 Mb region of chromosome 6p21 linked to disease. In a two-stage approach to fine mapping, linkage was evaluated in 385 affected sib-pair families using 13 evenly spaced polymorphic microsatellite markers. The whole 14 Mb showed strong linkage. Then, each marker was analysed for evidence of allelic association, revealing evidence of disease association at one marker located within the 95% confidence interval of 1.7 cM obtained by linkage. Analysis of an additional 12 markers flanking this marker revealed a highly specific region of 570 kb associated with disease ( P = 7.5 x 10(-35)), which included the HLA class II genes, known to be the primary determinants of IDDM1. The peak of association was as close as 85 kb centromeric of the disease-predisposing class II gene HLA-DQB1. We investigated the importance of the underlying inter-marker linkage disequilibrium, marker informativity and recombination for fine mapping and demonstrate that the majority of disease association in the region can be explained by linkage disequilibrium with the class II susceptibility genes. Recombination within the major histocompatibility complex was rare and nearly absent in the class III region. We demonstrate that fine mapping of a multifactorial disease gene is possible with high accuracy even in a region with extraordinary linkage disequilibrium across distances of several Mb. The results will be applicable to association studies of disease loci with lambda(s)values <2.7 except that much larger data sets will be required.

Adolescent↗

PubMed2006

Association analysis of the paraoxonase-1 gene with Alzheimer's disease.

Genetic variants in the paraoxonase (PON) gene cluster, particularly a single C/T promoter polymorphism (rs 705381) in the PON-1 gene, have recently been associated with Alzheimer's disease (AD). The T allele, in particular, presents an increased risk for the development of AD. Here, we investigate the potential role of this polymorphism in an Italian case-control population consisting of 306 sporadic AD patients and 275 controls, and also evaluate a possible interaction with the ApoE genotype. No association between the PON-1 polymorphism and AD was observed. The T allele frequency was slightly over-represented in AD patients compared to the controls, but this was far from being statistically significant. Our sample was evaluated to have 97.3% power to detect an OR of 2.0 (64.3% power with OR=1.5) at an alpha level of 0.05. No evidence of an interaction between the T risk-allele and the ApoE epsilon4 allele status and no effect of the PON-1 polymorphism on age at onset was detected. Our results do not support other studies indicating that the PON-1 promoter polymorphism plays a major role in AD, suggesting that other large studies are necessary to further elucidate the effect of PON on the development of the disease in the general population.

Aged↗

PubMed2025

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls. To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.

Journal Article↗

PubMed2006

Polymorphisms in FOXO gene family and association analysis with BMI.

Forkhead transcription factors of the FOXO subfamily are emerging as shared components of pathways that regulate a variety of cellular functions. In an effort to identify genetic polymorphisms in candidate genes to determine associations with BMI, we sequenced all exons of the FOXO genes (FOXO1a, FOXO3a, and FOXO4) and examined their associations with BMI in a Korean population (n = 734). Sixteen polymorphisms were identified in FOXO genes: three in FOXO1a, seven in FOXO3a, and six in FOXO4. Associations of FOXO polymorphisms with BMI were analyzed using multiple regression, adjusting for age and sex as covariates. One promoter single nucleotide polymorphism in the 5' flanking region of FOXO3a showed significant association with BMI, e.g., the lowest BMI (23.3 +/- 2.69 kg/m2) was discovered in individuals who were carrying T/T, intermediate BMI (26.6 +/- 3.14 kg/m2) was found in heterozygous individuals (C/T), and the highest BMI (27.2 +/- 3.47 kg/m2) occurred in individuals who were homozygous for the major allele (C/C; p = 0.01).

5' Flanking Region↗

PubMed2003

Genetic association analysis of KCNQ3 and juvenile myoclonic epilepsy in a South Indian population.

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsy that shows a complex pattern of inheritance. We have tested the association between JME phenotype and an intragenic marker in KCNQ3 by using the transmission disequilibrium test in 119 probands and their parents. Mutations in KCNQ3 are known to cause benign familial neonatal convulsions and are involved in the physiologically important M current in neurons. Our results provide suggestive evidence of allelic association between JME and KCNQ3 ( P-value=0.008) and raise an interesting possibility of a genetic contribution to JME, viz., of a gene that causes a monogenic form of human epilepsy.

Brain↗

PubMed2006

Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks.

The functional allele (577R) of ACTN3, which encodes human alpha-actinin-3, has been reported to be associated with elite athletic status and with response to resistance training, while the nonfunctional allele (577X) has been proposed as a candidate metabolically thrifty allele. In a study of 992 adolescent Greeks, we show that there is a significant association (P=0.003) between the ACTN3 R577X polymorphism and 40 m sprint time in males that accounts for 2.3% of phenotypic variance, with the 577R allele contributing to faster times in an additive manner. The R577X polymorphism is not associated with other power phenotypes related to 40 m sprint, nor with an endurance phenotype. Furthermore, the polymorphism is not associated with obesity-related phenotypes in our population, suggesting that the 577X allele is not a thrifty allele, and thus the persistence of this null allele must be explained in other terms.

Actinin↗

PubMed1999

NMR exchange broadening arising from specific low affinity protein self-association: analysis of nitrogen-15 nuclear relaxation for rat CD2 domain 1.

Nuclear spin relaxation monitored by heteronuclear NMR provides a useful method to probe the overall and internal molecular motion for biological macromolecules over a variety of time scales. Nitrogen-15 NMR relaxation parameters have been recorded for the N-terminal domain of the rat T-cell antigen CD2 (CD2d1) in a dilution series from 1.20 mM to 40 microM (pH 6.0, 25 degrees C). The data have been analysed within the framework of the model-free formalism of Lipari and Szabo to understand the molecular origin of severely enhanced transverse relaxation rates found for certain residues. These data revealed a strong dependence of the derived molecular correlation time tau c upon the CD2d1 protein concentration. Moreover, a number of amide NH resonances exhibited exchange broadening and chemical shifts both strongly dependent on protein concentration. These amide groups cluster on the major beta-sheet surface of CD2d1 that coincides with a major lattice contact in the X-ray structure of the intact ectodomain of rat CD2. The complete set of relaxation data fit well to an equilibrium monomer-dimer exchange model, yielding estimates of exchange rate constants (kON = 5000 M-1 s-1; kOFF = 7 s-1) and a dissociation constant (KD approximately 3-6 mM) that is consistent with the difficulty in detecting the weak interactions for this molecule by alternative biophysical methods. The self-association of CD2d1 is essentially invariant to changes in buffer composition and ionic strength and the associated relaxation phenomena cannot be explained as a result of neglecting anisotropic rotational diffusion in the analysis. These observations highlight the necessity to consider low affinity protein self-association interactions as a source of residue specific exchange phenomena in NMR spectra of macromolecular biomolecules, before the assignment of more elaborate intramolecular conformational mechanisms.

Animals↗

PubMed2007

Association analysis of the protein phosphatase 1 regulatory subunit 1B (PPP1R1B) gene with nicotine dependence in European- and African-American smokers.

The protein phosphatase 1 regulatory subunit 1B gene (PPP1R1B; also known as dopamine and cAMP-regulated phosphoprotein; DARPP32) is a target for the actions of dopamine. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, PPP1R1B is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within a region on chromosome 17 that demonstrated "suggestive linkage" to ND in our previous genome-wide scan. In the present study, we analyzed six single nucleotide polymorphisms (SNPs) within PPP1R1B for association with three ND measures: smoking quantity (SQ), the heaviness of smoking index (HSI), and the Fagerström Test for ND (FTND) score. Our sample consisted of 602 nuclear families of African-American (AA) or European-American (EA) origin. No significant associations were found for single SNPs after correction for multiple testing. However, haplotype analysis indicated that in the EA sample, the C-T-G-C haplotype formed by rs2271309-rs907094-rs3764352-rs3817160 with a frequency of 32.0% was significantly associated with SQ (Z = 2.50; P = 0.01), even after Bonferroni correction. No significant associations with haplotypes were found in the AA sample. In summary, our findings provide the first evidence for the potential involvement of PPP1R1B in the etiology of ND and further investigation is thus warranted.

Adult↗