0 Évaluations
ID

45091

Description

Principal Investigator: Demetrius M. Maraganore, Mayo Clinic, Rochester, MN, USA MeSH: Parkinson Disease https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000048 We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P.01 in tier 1) and 300 genomic control SNPs in 332 matched case-unrelated control pairs. We identified 11 SNPs that were associated with PD (P.01) in both tier 1 and tier 2 samples and had the same direction of effect. For these SNPs, we combined data from the case-unaffected sibling pair (tier 1) and case-unrelated control pair (tier 2) samples and employed a liberalization of the sibling transmission/disequilibrium test to calculate odds ratios, 95% confidence intervals, and P values. A SNP within the semaphorin 5A gene (SEMA5A) had the lowest combined P value (P=7.62E-6). The protein encoded by this gene plays an important role in neurogenesis and in neuronal apoptosis, which is consistent with existing hypotheses regarding PD pathogenesis. A second SNP tagged the PARK11 late-onset PD susceptibility locus (P=1.70E-5). In tier 2b, we also selected for genotyping additional SNPs that were borderline significant (P.05) in tier 1 but that tested a priori biological and genetic hypotheses regarding susceptibility to PD (n=941 SNPs). In analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values (P=9.07E-6; P=2.96E-5) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility. Note: The following instruments were used: 1)clinical assessments form and manual; 2) sibling screening form and manual; 3) unrelated control screening and manual; and 4) risk factors questionnaire and manual. All cases underwent #1, as did sibling controls screening positive (see below). Unrelated controls were not examined. All siblings underwent #2. All unrelated controls underwent #3. All subjects (cases, sibling controls, and unrelated controls) underwent #4. Any publications using the data are to cite the original American Journal of Human Genetics article (Maraganore et al., 2005). Investigators using the data collection instruments are to acknowledge Drs. Maraganore and Rocca, and cite grants ES-10751 and NS-33978.

Lien

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000048

Mots-clés

Versions (1)
  1. 22/08/2022 22/08/2022 - Tabea Kampen
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Demetrius M. Maraganore, Mayo Clinic, Rochester, MN, USA

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22 août 2022

DOI

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Licence

Creative Commons BY 4.0
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    44963_dbGaP phs000048 Mayo-Perlegen LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) Collaboration

    Anglais

    Eligibility Criteria

    3 Formulaires  
    Inclusion and exclusion criteria
    Description

    Inclusion and exclusion criteria

    Alias
    UMLS CUI [1,1]
    C1516637
    Criteria for Cases: Cases were enrolled prospectively from the clinical practice of the Department of Neurology of the Mayo Clinic in Rochester, MN, from June 1996 through May 2004. They all resided within Minnesota or one of the surrounding four states (Wisconsin, Iowa, South Dakota, or North Dakota). All cases underwent a standardized clinical assessment performed by a neurologist sub-specialized in movement disorders. Cases had at least two of four cardinal signs of parkinsonism (rest tremor, rigidity, bradykinesia, and/or postural instability) and no features atypical for PD (such as unexplained upper motor neuron signs or cerebellar signs). When non-motor manifestations such as dysautonomia or dementia were present, they were mild and occurred late in the disease course. Subjects with secondary causes of parkinsonism (e.g., history of neuroleptic exposure, encephalitis, or multiple strokes) were excluded. All patients treated with a daily dosage total of 1 g of levodopa (in combination with carbidopa) had a more than minimal improvement in parkinsonism symptoms and signs.
    Description

    Elig.phs000048.v1.p1.1

    Type de données

    boolean

    Alias
    UMLS CUI [1,1]
    C1516637
    UMLS CUI [1,2]
    C1512693
    UMLS CUI [1,3]
    C1706256
    UMLS CUI [2,1]
    C0237096
    UMLS CUI [2,2]
    C0027853
    UMLS CUI [2,3]
    C2733447
    UMLS CUI [2,4]
    C1457887
    UMLS CUI [2,5]
    C0023570
    UMLS CUI [2,6]
    C0184511
    UMLS CUI [3,1]
    C0680251
    UMLS CUI [3,2]
    C0030569
    UMLS CUI [3,3]
    C4302185
    Criteria for Controls: Unaffected siblings of cases, matched on gender when able then on closest age at study (tier 1); or unrelated population controls, matched on gender and age at study (tier 2). All controls screened negative for parkinsonism via telephone interview, or were confirmed to not have parkinsonism via clinical assessment.
    Description

    Elig.phs000048.v1.p1.2

    Type de données

    boolean

    Alias
    UMLS CUI [1,1]
    C0009932
    UMLS CUI [1,2]
    C1512693
    UMLS CUI [2,1]
    C0037047
    UMLS CUI [2,2]
    C2986417
    UMLS CUI [2,3]
    C0079399
    UMLS CUI [2,4]
    C0001779
    UMLS CUI [2,5]
    C0150103
    UMLS CUI [2,6]
    C2733447
    UMLS CUI [2,7]
    C1457887
    UMLS CUI [2,8]
    C0332268
    UMLS CUI [3,1]
    C2348561
    UMLS CUI [3,2]
    C0445356
    UMLS CUI [3,3]
    C0079399
    UMLS CUI [3,4]
    C0001779
    UMLS CUI [3,5]
    C0150103
    UMLS CUI [3,6]
    C2733447
    UMLS CUI [3,7]
    C1457887
    UMLS CUI [3,8]
    C0332268
    Retour au début de la page

    Similar models

    Eligibility Criteria

    3 Formulaires
    Name
    Type
    Description | Question | Decode (Coded Value)
    Type de données
    Alias
    Item Group
    Inclusion and exclusion criteria
    C1516637 (UMLS CUI [1,1])
    Elig.phs000048.v1.p1.1
    Item
    Criteria for Cases: Cases were enrolled prospectively from the clinical practice of the Department of Neurology of the Mayo Clinic in Rochester, MN, from June 1996 through May 2004. They all resided within Minnesota or one of the surrounding four states (Wisconsin, Iowa, South Dakota, or North Dakota). All cases underwent a standardized clinical assessment performed by a neurologist sub-specialized in movement disorders. Cases had at least two of four cardinal signs of parkinsonism (rest tremor, rigidity, bradykinesia, and/or postural instability) and no features atypical for PD (such as unexplained upper motor neuron signs or cerebellar signs). When non-motor manifestations such as dysautonomia or dementia were present, they were mild and occurred late in the disease course. Subjects with secondary causes of parkinsonism (e.g., history of neuroleptic exposure, encephalitis, or multiple strokes) were excluded. All patients treated with a daily dosage total of 1 g of levodopa (in combination with carbidopa) had a more than minimal improvement in parkinsonism symptoms and signs.
    boolean
    C1516637 (UMLS CUI [1,1])
    C1512693 (UMLS CUI [1,2])
    C1706256 (UMLS CUI [1,3])
    C0237096 (UMLS CUI [2,1])
    C0027853 (UMLS CUI [2,2])
    C2733447 (UMLS CUI [2,3])
    C1457887 (UMLS CUI [2,4])
    C0023570 (UMLS CUI [2,5])
    C0184511 (UMLS CUI [2,6])
    C0680251 (UMLS CUI [3,1])
    C0030569 (UMLS CUI [3,2])
    C4302185 (UMLS CUI [3,3])
    Elig.phs000048.v1.p1.2
    Item
    Criteria for Controls: Unaffected siblings of cases, matched on gender when able then on closest age at study (tier 1); or unrelated population controls, matched on gender and age at study (tier 2). All controls screened negative for parkinsonism via telephone interview, or were confirmed to not have parkinsonism via clinical assessment.
    boolean
    C0009932 (UMLS CUI [1,1])
    C1512693 (UMLS CUI [1,2])
    C0037047 (UMLS CUI [2,1])
    C2986417 (UMLS CUI [2,2])
    C0079399 (UMLS CUI [2,3])
    C0001779 (UMLS CUI [2,4])
    C0150103 (UMLS CUI [2,5])
    C2733447 (UMLS CUI [2,6])
    C1457887 (UMLS CUI [2,7])
    C0332268 (UMLS CUI [2,8])
    C2348561 (UMLS CUI [3,1])
    C0445356 (UMLS CUI [3,2])
    C0079399 (UMLS CUI [3,3])
    C0001779 (UMLS CUI [3,4])
    C0150103 (UMLS CUI [3,5])
    C2733447 (UMLS CUI [3,6])
    C1457887 (UMLS CUI [3,7])
    C0332268 (UMLS CUI [3,8])
    Retour au début de la page 

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