Evidence map›Paper›PMID 27123490›Full record

ArticleNeurology. Genetics2016

DNA variants in CACNA1C modify Parkinson disease risk only when vitamin D level is deficient.

Liyong Wang, Lizmarie Maldonado, Gary W Beecham, Eden R Martin, Marian L Evatt, James C Ritchie, Jonathan L Haines, Cyrus P Zabetian, Haydeh Payami, Margaret A Pericak-Vance and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Epigenomic profile of GBA1 in Parkinson's disease.Parkinsonism & related disorders · 2025
    Article
  4. Disease-modifying, multidimensional efficacy of putaminal CaMolecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Liyong WangJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Lizmarie MaldonadoJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Gary W BeechamJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Eden R MartinJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Marian L EvattJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
James C RitchieJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Jonathan L HainesJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Cyrus P ZabetianJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Haydeh PayamiJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Jeffery M VanceJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
William K ScottJohn P. Hussman Institute for Human Genomics (L.W., L.M., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), and Dr. John T. Macdonald Foundation Department of Human Genetics (L.W., G.W.B., E.R.M., M.A.P.-V., J.M.V., W.K.S.), Miller School of Medicine, University of Miami, FL; Departments of Neurology (M.L.E.), and Pathology (J.C.R.), Emory University, Atlanta, GA; Department of Epidemiology and Biostatistics and Institute for Computational Biology (J.L.H.), Case Western Reserve University, Cleveland, OH; Veterans Affairs Puget Sound Health Care System and Department of Neurology (C.P.Z.), University of Washington, Seattle, WA; and Department of Neurology (H.P.), University of Alabama at Birmingham, AL.
Case Western Reserve University · USUniversity of Washington · USVA Puget Sound Health Care System · USEmory University · US

Funding

Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Vitamin D Concentration, Genetic Modifiers, and Parkinson DiseaseP50NS071674 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI VANCE, JEFFERY MARVIN · 2010 to 2015
$10.2M
Pharmacogenomics of Parkinson's DiseaseR01NS067469 · NINDS · WADSWORTH CENTER · PI PAYAMI, HAYDEH · 2010 to 2014
$2.5M
Using Multiplex Families to map Genes that Modify Susceptibility and Age at OnsetR01NS065070 · NINDS · UNIVERSITY OF WASHINGTON · PI ZABETIAN, CYRUS P · 2009 to 2012
$2.0M
Genetic Risk Factors for Parkinson's DiseaseI01BX000531 · VA · VA PUGET SOUND HEALTHCARE SYSTEM · PI ZABETIAN, CYRUS P · 2009 to 2013
–
BLRD VA I01 BX000531NINDS NIH HHS P50 NS062684NINDS NIH HHS P50 NS071674NINDS NIH HHS R01 NS065070NINDS NIH HHS R01 NS067469
6 · The paper itself

Abstract

objectiveTo evaluate the association between the genetic variants in CACNA1C, which encodes the α1 subunit of the L-type voltage-sensitive calcium channel (LVSCC) and Parkinson disease (PD) while accounting for interactions with vitamin D concentration.

methodsTwo independent case-control data sets (478 cases and 431 controls; 482 cases and 412 controls) were used. Joint effects of single nucleotide polymorphisms (SNPs) and SNP-vitamin D interaction were analyzed by comparing models containing vitamin D deficiency, SNP genotypes, SNP-vitamin D interaction, and covariates to a restricted model with only vitamin D deficiency and covariates. Meta-analysis was used to combine the joint effects in the 2 data sets. Analysis was stratified by vitamin D deficiency to demonstrate the pattern of SNP-vitamin D interaction.

resultsVitamin D deficiency was associated with PD in both data sets (odds ratio [OR] = 1.9-2.7, p ≤ 0.009). SNP rs34621387 demonstrated a significant joint effect (meta-analysis, p = 7.5 × 10(-5); Bonferroni corrected, p = 0.02). The G allele at rs34621387 is associated with PD in vitamin D-deficient individuals in both data sets (OR = 2.0-2.1, confidence interval = 1.3-3.5, p = 0.002) but is not associated with PD in vitamin D-nondeficient individuals (p > 0.8 in both data sets).

conclusionsPrevious studies suggest that vitamin D deficiency is associated with PD and sustained opening of LVSCC contributes to the selective vulnerability of dopaminergic neurons in PD. Our data demonstrate that the association between genetic variations in CACNA1C and PD depends on vitamin D deficiency, providing one potential mechanism underlying the association between vitamin D deficiency and PD.

Identifiers

PMID27123490
PMCPMC4830205
OpenAlexW2342174107

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.