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Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes.
Alfradique-Dunham, Isabel; Al-Ouran, Rami; von Coelln, Rainer; Blauwendraat, Cornelis; Hill, Emily; Luo, Lan; Stillwell, Amanda; Young, Emily; Kaw, Anita; Tan, Manuela; Liao, Calwing; Hernandez, Dena; Pihlstrom, Lasse; Grosset, Donald; Shulman, Lisa M; Liu, Zhandong; Rouleau, Guy A; Nalls, Mike; Singleton, Andrew B; Morris, Huw; Jankovic, Joseph; Shulman, Joshua M.
Afiliação
  • Alfradique-Dunham I; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Al-Ouran R; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • von Coelln R; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Blauwendraat C; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Hill E; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Luo L; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Stillwell A; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Young E; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Kaw A; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Tan M; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Liao C; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Hernandez D; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Pihlstrom L; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Grosset D; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Shulman LM; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Liu Z; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Rouleau GA; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Nalls M; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Singleton AB; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Morris H; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Jankovic J; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
  • Shulman JM; Department of Neurology (I.A.-D., E.H., L.L., A.S., E.Y., A.K., J.J., J.M.S.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (R.A.-O., Z.L.), Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute (R.A.-O., Z.L., J.M.S.), Texas Childrens Hospi
Neurol Genet ; 7(2): e557, 2021 Apr.
Article em En | MEDLINE | ID: mdl-33987465
ABSTRACT

OBJECTIVE:

To discover genetic determinants of Parkinson disease (PD) motor subtypes, including tremor dominant (TD) and postural instability/gait difficulty (PIGD) forms.

METHODS:

In 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining 2 complementary outcome traits derived from the Unified Parkinson's Disease Rating Scale, including dichotomous motor subtype (TD vs PIGD) or a continuous tremor/PIGD score ratio. Logistic or linear regression models were adjusted for sex, age at onset, disease duration, and 5 ancestry principal components, followed by meta-analysis.

RESULTS:

Among 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, including GPNMB (rs199351, p subtype = 0.01, p ratio = 0.03), SH3GL2 (rs10756907, p subtype = 0.02, p ratio = 0.01), HIP1R (rs10847864, p subtype = 0.02), RIT2 (rs12456492, p subtype = 0.02), and FBRSL1 (rs11610045, p subtype = 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (p = 0.026, ß = -0.04, 95% confidence interval = -0.07-0). Based on top results of our GWAS, we identify a novel suggestive association at the STK32B locus (rs2301857, p ratio = 6.6 × 10-7), which harbors an independent risk allele for essential tremor.

CONCLUSIONS:

Multiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant at STK32B suggests a possible overlap between genetic risk for essential tremor and tremor-dominant PD.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article