The Genetics of Parkinson’s Disease

Year 2024, Volume: 34 Issue: 1, 136 - 143, 29.02.2024

Zeliha Yücel , Levent Şimşek , Emine Berrin Yüksel

https://doi.org/10.54005/geneltip.1337447

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Approximately 15% of PD patients have a family history of the disease in one or more first-degree relatives, and 5-10% of PD cases exhibit a classical Mendelian inheritance pattern. In 1997, the heritable transmission of PD was first documented. Recent studies have found 90 independent genome-wide signals at 78 loci that may be associated with PD. The identification of genes linked to PD and their functions has uncovered novel biological pathways and treatment options that play a role in the development of PD. In this article, it is aimed to review up-to-date information on the genetics of PD.

Keywords

Parkinson’s Disease, Inheritance, Autosomal Dominant, Autosomal Recessive

Parkinson Hastalığı Genetiği

Abstract

Parkinson hastalığı (PH), dünya çapında en yaygın nörodejeneratif hastalıklardan biridir. PH hastalarının yaklaşık %15'inde bir veya daha fazla birinci derece akrabada hastalık öyküsü vardır ve PH vakalarının %5-10'u klasik Mendel kalıtım modeli sergiler. 1997'de, PH'nın kalıtsal geçişi ilk kez belgelenmiştir. Son yapılan araştırmalarda, PD ile ilişkili olabilecek 78 lokusta 90 bağımsız genom çapında sinyal bulunmuştur. PH ile bağlantılı genlerin ve bunların işlevlerinin tanımlanması, PH gelişiminde rol oynayan yeni biyolojik yolları ve tedavi seçeneklerini ortaya çıkmasını sağlamıştır. Bu yazıda Parkinson hastalığının genetiği ile ilgili güncel bilgilerin gözden geçirilmesi amaçlanmıştır.

Keywords

Parkinson Hastalığı, Kalıtım, Otozomal Dominant, Otozomal Resesif

References

• Kalia L V, Lang AE. Parkinson’s disease. The Lancet. 2015 Aug;386(9996):896–912.
• Rocca WA. The burden of Parkinson’s disease: a worldwide perspective. Lancet Neurol. 2018 Nov;17(11):928–9.
• Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan 27;27(1):27–42.
• Yalçın Çakmaklı G EB. Parkinson Hastalığında Patogenez. Türkiye Klinikleri. 2021;5–10.
• Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr 1;79(4):368–76.
• Lesage S, Brice A. Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet. 2009 Apr 15;18(R1):R48–59.
• Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the α-Synuclein Gene Identified in Families with Parkinson’s Disease. Science (1979). 1997 Jun 27;276(5321):2045–7.
• Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019 Dec;18(12):1091–102.
• Marras C, Lang A, van de Warrenburg BP, Sue CM, Tabrizi SJ, Bertram L, et al. Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. Movement Disorders. 2016 Apr;31(4):436–57.
• Cook Shukla L SJFJ et al. Parkinson Disease Overview.2004 May 25 [Updated 2019 Jul 25]. In: In: Adam MP MGPR et al. , editors. G [Internet]., editor. GeneReviews® [Internet] Seattle (WA): University of Washington, Seattle; 1993-2023 [Internet]. [cited 2023 Jul 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1223/
• Bonini NM, Giasson BI. Snaring the Function of α-Synuclein. Cell. 2005 Nov;123(3):359–61.
• Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N, et al. G51D α-synuclein mutation causes a novel Parkinsonian-pyramidal syndrome. Ann Neurol. 2013 Apr;73(4):459–71.
• Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of α-synuclein causes parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164–73.
• Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, et al. AlaSOPro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet. 1998 Feb;18(2):106–8.
• Kiely AP, Asi YT, Kara E, Limousin P, Ling H, Lewis P, et al. α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy? Acta Neuropathol. 2013 May 12;125(5):753–69.
• Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, et al. Genomic investigation of α-synuclein multiplication and parkinsonism. Ann Neurol. 2008 Jun;63(6):743–50.
• Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. α-Synuclein Locus Triplication Causes Parkinson’s Disease. Science (1979). 2003 Oct 31;302(5646):841–841.
• Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol. 2002 Mar;51(3):296–301.
• Wallings R, Manzoni C, Bandopadhyay R. Cellular processes associated with LRRK2 function and dysfunction. FEBS Journal. 2015 Aug;282(15):2806–26.
• Cookson MR. LRRK2 Pathways Leading to Neurodegeneration. Curr Neurol Neurosci Rep. 2015 Jul 26;15(7):42.
• Lee HJ, Khoshaghideh F, Patel S, Lee SJ. Clearance of α-Synuclein Oligomeric Intermediates via the Lysosomal Degradation Pathway. The Journal of Neuroscience. 2004 Feb 25;24(8):1888–96.
• Lee AJ, Wang Y, Alcalay RN, Mejia-Santana H, Saunders-Pullman R, Bressman S, et al. Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. Movement Disorders. 2017 Oct;32(10):1432–8.
• Marder K, Wang Y, Alcalay RN, Mejia-Santana H, Tang MX, Lee A, et al. Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium. Neurology. 2015 Jul 7;85(1):89–95.
• Healy DG, Falchi M, O’Sullivan SS, Bonifati V, Durr A, Bressman S, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 2008 Jul;7(7):583–90.
• Simpson C, Vinikoor-Imler L, Nassan FL, Shirvan J, Lally C, Dam T, et al. Prevalence of ten LRRK2 variants in Parkinson’s disease: A comprehensive review. Parkinsonism Relat Disord. 2022 May;98:103–13.
• Trinh J, Zeldenrust FMJ, Huang J, Kasten M, Schaake S, Petkovic S, et al. Genotype-phenotype relations for the Parkinson’s disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Movement Disorders. 2018 Dec;33(12):1857–70.
• Hanss Z, Larsen SB, Antony P, Mencke P, Massart F, Jarazo J, et al. Mitochondrial and Clearance Impairment in p. <scp>D620N VPS35</scp> Patient‐Derived Neurons. Movement Disorders. 2021 Mar 3;36(3):704–15.
• Bono K, Hara-Miyauchi C, Sumi S, Oka H, Iguchi Y, Okano HJ. Endosomal dysfunction in iPSC-derived neural cells from Parkinson’s disease patients with VPS35 D620N. Mol Brain. 2020 Dec 8;13(1):137.
• Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, et al. VPS35 Mutations in Parkinson Disease. The American Journal of Human Genetics. 2011 Jul;89(1):162–7.
• Nuytemans K, Bademci G, Inchausti V, Dressen A, Kinnamon DD, Mehta A, et al. Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology. 2013 Mar 12;80(11):982–9.
• Dulski J, Uitti RJ, Ross OA, Wszolek ZK. Genetic architecture of Parkinson’s disease subtypes – Review of the literature. Front Aging Neurosci. 2022 Oct 20;14.
• National Center for Biotechnology Information (NCBI) United States National Library of Medicine (NLM). GBA1 glucosylceramidase beta 1 [ Homo sapiens (human) [Internet]. 2023 [cited 2023 May 23]. Available from: https://www.ncbi.nlm.nih.gov/gene/2629
• Brady RO, Kanfer JN, Bradley RM, Shapiro D. Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher’s disease. Journal of Clinical Investigation. 1966 Jul 1;45(7):1112–5.
• Goker-Alpan O. Parkinsonism among Gaucher disease carriers. J Med Genet. 2004 Dec 1;41(12):937–40.
• Neudorfer O, Giladi N, Elstein D, Abrahamov A, Turezkite T, Aghai E, et al. Occurrence of Parkinson’s syndrome in type 1 Gaucher disease. QJM. 1996 Sep 1;89(9):691–4.
• Gan-Or Z, Amshalom I, Kilarski LL, Bar-Shira A, Gana-Weisz M, Mirelman A, et al. Differential effects of severe vs mild GBA mutations on Parkinson disease. Neurology. 2015 Mar 3;84(9):880–7.
• Mata IF, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, et al. GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson’s disease. Movement Disorders. 2016 Jan;31(1):95–102.
• Lopez G, Kim J, Wiggs E, Cintron D, Groden C, Tayebi N, et al. Clinical course and prognosis in patients with Gaucher disease and parkinsonism. Neurol Genet. 2016 Apr 4;2(2):e57.
• Winder-Rhodes SE, Evans JR, Ban M, Mason SL, Williams-Gray CH, Foltynie T, et al. Glucocerebrosidase mutations influence the natural history of Parkinson’s disease in a community-based incident cohort. Brain. 2013 Feb;136(2):392–9.
• Brodeur J, Thériault C, Lessard-Beaudoin M, Marcil A, Dahan S, Lavoie C. LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer’s disease. Mol Neurodegener. 2012 Dec 26;7(1):31.
• Quadri M, Mandemakers W, Grochowska MM, Masius R, Geut H, Fabrizio E, et al. LRP10 genetic variants in familial Parkinson’s disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study. Lancet Neurol. 2018 Jul;17(7):597–608.
• Pihlstrøm L, Schottlaender L, Chelban V, Houlden H, Al-Sarraj S, Arzberger T, et al. LRP10 in α-synucleinopathies. Lancet Neurol. 2018 Dec;17(12):1033–4.
• National Center for Biotechnology Information (NCBI) United States National Library of Medicine (NLM). Eif4g1 eukaryotic translation initiation factor 4, gamma 1 [ Mus musculus (house mouse) ].
• Chartier-Harlin MC, Dachsel JC, Vilariño-Güell C, Lincoln SJ, Leprêtre F, Hulihan MM, et al. Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease. The American Journal of Human Genetics. 2011 Sep;89(3):398–406.
• Chartier-Harlin MC, Dachsel J, Hulihan M, Kachergus J, Lepretre F, Le Rhun E, et al. P2.206 EIF4G1 mutations in familial parkinsonism. Parkinsonism Relat Disord. 2009 Dec;15:S145–6.
• Huttenlocher J, Krüger R, Capetian P, Lohmann K, Brockmann K, Csoti I, et al. EIF4G1 is neither a strong nor a common risk factor for Parkinson’s disease: evidence from large European cohorts: Table1. J Med Genet. 2015 Jan;52(1):37–41.
• Saini P, Rudakou U, Yu E, Ruskey JA, Asayesh F, Laurent SB, et al. Association study of DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 with Parkinson’s disease. Neurobiol Aging. 2021 Apr;100:119.e7-119.e13.
• Yoshii SR, Kishi C, Ishihara N, Mizushima N. Parkin Mediates Proteasome-dependent Protein Degradation and Rupture of the Outer Mitochondrial Membrane. Journal of Biological Chemistry. 2011 Jun;286(22):19630–40.
• Seirafi M, Kozlov G, Gehring K. Parkin structure and function. FEBS J. 2015 Jun 16;282(11):2076–88.
• Ishikawa A, Takahashi H. Clinical and neuropathological aspects of autosomal recessive juvenile parkinsonism. J Neurol. 1998 Sep 10;245(S3):P4–9.
• Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, et al. Association between Early-Onset Parkinson’s Disease and Mutations in the Parkin Gene. New England Journal of Medicine. 2000 May 25;342(21):1560–7.
• Klein C, Lohmann-Hedrich K. Impact of recent genetic findings in Parkinson’s disease. Curr Opin Neurol. 2007 Aug;20(4):453–64.
• Cazeneuve C, Sân C, Ibrahim SA, Mukhtar MM, Kheir MM, LeGuern E, et al. A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease. Neurogenetics. 2009 Jul 12;10(3):265–70.
• Lesage S, Lohmann E, Tison F, Durif F, Durr A, Brice A. Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. J Med Genet. 2007 Oct 26;45(1):43–6.
• Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL, Hubble JP, et al. Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Ann Neurol. 2003 May;53(5):624–9.
• MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 2017 Jan 4;45(D1):D896–901.
• Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, et al. Association between Early-Onset Parkinson’s Disease and Mutations in the Parkin Gene. New England Journal of Medicine. 2000 May 25;342(21):1560–7.
• Kay DM, Moran D, Moses L, Poorkaj P, Zabetian CP, Nutt J, et al. Heterozygous parkin point mutations are as common in control subjects as in Parkinson’s patients. Ann Neurol. 2007 Jan;61(1):47–54.
• Yu E, Rudakou U, Krohn L, Mufti K, Ruskey JA, Asayesh F, et al. Analysis of Heterozygous PRKN Variants and Copy‐Number Variations in Parkinson’s Disease. Movement Disorders. 2021 Jan 24;36(1):178–87.
• Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway regulates mitochondrial morphology. Proceedings of the National Academy of Sciences. 2008 Feb 5;105(5):1638–43.
• Cazeneuve C, Sân C, Ibrahim SA, Mukhtar MM, Kheir MM, LeGuern E, et al. A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease. Neurogenetics. 2009 Jul 12;10(3):265–70.
• Camargos ST, Dornas LO, Momeni P, Lees A, Hardy J, Singleton A, et al. Familial Parkinsonism and early onset Parkinson’s disease in a Brazilian movement disorders clinic: Phenotypic characterization and frequency of SNCA , PRKN , PINK1 , and LRRK2 mutations. Movement Disorders. 2009 Apr 15;24(5):662–6.
• Klein C, Westenberger A. Genetics of Parkinson’s Disease. Cold Spring Harb Perspect Med. 2012 Jan 1;2(1):a008888–a008888.
• Junn E, Taniguchi H, Jeong BS, Zhao X, Ichijo H, Mouradian MM. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proceedings of the National Academy of Sciences. 2005 Jul 5;102(27):9691–6.
• Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
• Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
• Annesi G, Savettieri G, Pugliese P, D’Amelio M, Tarantino P, Ragonese P, et al. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol. 2005 Nov;58(5):803–7.
• Pankratz N, Pauciulo MW, Elsaesser VE, Marek DK, Halter CA, Wojcieszek J, et al. Mutations in DJ-1 are rare in familial Parkinson disease. Neurosci Lett. 2006 Nov;408(3):209–13.
• Annesi G, Savettieri G, Pugliese P, D’Amelio M, Tarantino P, Ragonese P, et al. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol. 2005 Nov;58(5):803–7.
• Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW. The role of pathogenic DJ-1 mutations in Parkinson’s disease. Ann Neurol. 2003 Sep;54(3):283–6.
• Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
• Yim YI, Sun T, Wu LG, Raimondi A, De Camilli P, Eisenberg E, et al. Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout mice. Proceedings of the National Academy of Sciences. 2010 Mar 2;107(9):4412–7.
• Elsayed LEO, Drouet V, Usenko T, Mohammed IN, Hamed AAA, Elseed MA, et al. A Novel Nonsense Mutation in DNAJC6 Expands the Phenotype of Autosomal-Recessive Juvenile-Onset Parkinson’s Disease. Ann Neurol. 2016 Feb;79(2):335–7.
• Olgiati S, Quadri M, Fang M, Rood JPMA, Saute JA, Chien HF, et al. DNAJC6 Mutations Associated With Early-Onset Parkinson’s Disease. Ann Neurol. 2016 Feb;79(2):244–56.
• Dehay B, Martinez-Vicente M, Ramirez A, Perier C, Klein C, Vila M, et al. Lysosomal dysfunction in Parkinson disease. Autophagy. 2012 Sep 14;8(9):1389–91.
• Ramirez A, Heimbach A, Gründemann J, Stiller B, Hampshire D, Cid LP, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet. 2006 Oct 10;38(10):1184–91.
• Brüggemann N, Hagenah J, Reetz K, Schmidt A, Kasten M, Buchmann I, et al. Recessively Inherited Parkinsonism. Arch Neurol. 2010 Nov 1;67(11).
• Fonzo AD, Dekker MCJ, Montagna P, Baruzzi A, Yonova EH, Guedes LC, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology. 2009 Jan 20;72(3):240–5.
• Davison C. Pallido-Pyramidal Disease. J Neuropathol Exp Neurol. 1954 Jan;13(1):50–9.
• National Center for Biotechnology Information (NCBI) United States National Library of Medicine (NLM). PLA2G6 phospholipase A2 group VI [ Homo sapiens (human) ] [Internet]. [cited 2023 May 27]. Available from: https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=8398
• Gregory A KMME et al. PLA2G6-Associated Neurodegeneration. . In: GeneReviews®. 2008.
• McPherson PS, Czernik AJ, Chilcote TJ, Onofri F, Benfenati F, Greengard P, et al. Interaction of Grb2 via its Src homology 3 domains with synaptic proteins including synapsin I. Proceedings of the National Academy of Sciences. 1994 Jul 5;91(14):6486–90.
• Cremona O, Nimmakayalu M, Haffner C, Bray-Ward P, Ward DC, De Camilli P. Assignment of SYNJ1 to human chromosome 21q22.2 and Synj12; to the murine homologous region on chromosome 16C3–4 by in situ hybridization. Cytogenet Genome Res. 2000;88(1–2):89–90.
• Al Zaabi N, Al Menhali N, Al-Jasmi F. SYNJ1 gene associated with neonatal onset of neurodegenerative disorder and intractable seizure. Mol Genet Genomic Med. 2018 Jan;6(1):109–13.
• Dyment DA, Smith AC, Humphreys P, Schwartzentruber J, Beaulieu CL, Bulman DE, et al. Homozygous nonsense mutation in SYNJ1 associated with intractable epilepsy and tau pathology. Neurobiol Aging. 2015 Feb;36(2):1222.e1-1222.e5.
• Hardies K, Cai Y, Jardel C, Jansen AC, Cao M, May P, et al. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline. Brain. 2016 Sep;139(9):2420–30.
• Lesage S, Mangone G, Tesson C, Bertrand H, Benmahdjoub M, Kesraoui S, et al. Clinical Variability of SYNJ1-Associated Early-Onset Parkinsonism. Front Neurol. 2021 Mar 25;12.
• Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, Goto S, et al. Reduced Neuron-Specific Expression of the TAF1 Gene Is Associated with X-Linked Dystonia-Parkinsonism. The American Journal of Human Genetics. 2007 Mar;80(3):393–406.
• Lee L, Pascasio FM, Fuentes FD, Viterbo G. Torsion dystonia in Panay, Philippines. Adv Neurol. 1976;14:137–51.
• Johnston AW,, McKusick VA. Sex-linked recessive inheritance in spastic paraplegia and parkinsonism. In: Gedda L, editor. Proceedings of the Second International Congress on Human Genetics,. 1961. p. 6–12.
• Lobo Ingrid. Environmental Influences on Gene Expression. In: Hoopes Laura, editor. GENE EXPRESSION AND REGULATION. 2008.
• Day JO, Mullin S. The Genetics of Parkinson’s Disease and Implications for Clinical Practice. Genes (Basel). 2021 Jun 30;12(7):1006.
• Davis AA, Andruska KM, Benitez BA, Racette BA, Perlmutter JS, Cruchaga C. Variants in GBA , SNCA , and MAPT influence Parkinson disease risk, age at onset, and progression. Neurobiol Aging. 2016 Jan;37:209.e1-209.e7.
• Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet. 2014 Sep 1;46(9):989–93.
• International Schizophrenia Consortium; Shaun M Purcell NRWJLSPMVMCOPFSPS. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009 Aug 1;460(7256):748–52.
• Escott‐Price V, Nalls MA, Morris HR, Lubbe S, Brice A, Gasser T, et al. Polygenic risk of Parkinson disease is correlated with disease age at onset. Ann Neurol. 2015 Apr 13;77(4):582–91.
• Susan Searles Nielsen 1 TKBLGGFMFWLJGMFPDSHC. Genotype and age at Parkinson disease diagnosis. Int J Mol Epidemiol Genet . 2013;4(1):61–9.
• Cook L, Schulze J, Kopil C, Hastings T, Naito A, Wojcieszek J, et al. Genetic Testing for Parkinson Disease. Neurol Clin Pract. 2021 Feb;11(1):69–77.