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@ARTICLE{Liu:164533,
      author       = {Liu, Hui and Dehestani, Mohammad and Blauwendraat, Cornelis
                      and Makarious, Mary B and Leonard, Hampton L and Kim,
                      Jonggeol J and Schulte, Claudia and Noyce, Alastair and
                      Jacobs, Benjamin M and Foote, Isabelle and Sharma, Manu and
                      Genetics, Comprehensive Unbiased Risk factor Assessment for
                      and Nalls, Mike and Singleton, Andrew and Gasser, Thomas and
                      Bandres-Ciga, Sara},
      collaboration = {Consortium, International Parkinson's Disease Genomics and
                      Disease, Environment in Parkinson's},
      title        = {{P}olygenic resilience modulates the penetrance of
                      {P}arkinson's disease genetic risk factors.},
      journal      = {Annals of neurology},
      volume       = {92},
      number       = {2},
      issn         = {0364-5134},
      address      = {Hoboken, NJ},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2022-01082},
      pages        = {270-278},
      year         = {2022},
      note         = {CC BY-NC-ND},
      abstract     = {The aim of the current study is to understand why some
                      individuals avoid developing Parkinson's disease (PD) in
                      spite of being at relatively high genetic risk, using the
                      largest datasets of individual-level genetic data
                      available.We calculated polygenic risk score to identify
                      controls and matched PD cases with the highest burden of
                      genetic risk for PD in the discovery cohort (IPDGC, 7,204 PD
                      cases and 9,412 controls) and validation cohorts
                      (COURAGE-PD, 8,968 cases and 7,598 controls; UKBB, 2,639 PD
                      cases and 14,301 controls; AMP-PD, 2,248 cases and 2,817
                      controls). A genome-wide association study meta-analysis was
                      performed on these individuals to understand genetic
                      variation associated with resistance to disease. We further
                      constructed a polygenic resilience score, performed MAGMA
                      gene-based analyses and functional enrichment analyses.A
                      higher polygenic resilience score was associated with a
                      lower risk for PD (Beta= -0.054, SE = 0.022; P = 0.013).
                      Although no single locus reached genome-wide significance,
                      MAGMA gene-based analyses nominated TBCA as a putative gene.
                      Furthermore, we estimated the narrow-sense heritability
                      associated with resilience to PD (h2 = 0.081, SE = 0.035, P
                      = 0.0003). Subsequent functional enrichment analysis
                      highlighted histone methylation as potential pathway
                      harboring resilience alleles that could mitigate the effects
                      of PD risk loci.The present study represents a novel and
                      comprehensive assessment of heritable genetic variation
                      contributing to PD resistance. We show that a genetic
                      resilience score can modify the penetrance of PD genetic
                      risk factors and therefore protect individuals carrying a
                      high-risk genetic burden from developing PD. This article is
                      protected by copyright. All rights reserved.},
      keywords     = {Parkinson's disease (Other) / genetics (Other) / polygenic
                      risk (Other) / resilience (Other)},
      cin          = {AG Gasser / Tübingen common / Ext HIH},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)6000018 /
                      I:(DE-2719)5000057},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35599344},
      doi          = {10.1002/ana.26416},
      url          = {https://pub.dzne.de/record/164533},
}