Neurological Sciences

, Volume 39, Issue 12, pp 2061–2069 | Cite as

An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson’s disease

  • Xu Liu
  • Ruixia Zhu
  • Tongling Xiao
  • Qu Li
  • Ying Zhu
  • Zhiyi HeEmail author
Original Article


Large-scale genome-wide association study (GWAS) has identified that the alpha-synuclein (SNCA) rs11931074 polymorphism is associated with Parkinson’s disease (PD) susceptibility in individuals of Japanese descent. Subsequently, a number of replication studies have been performed in Asian and Caucasian populations. However, the results remain controversial due to the relatively small sample sizes and genetic heterogeneity. Here, to overcome the limitations of individual studies, we reevaluated this association with data from 33 independent studies involving 15,368 patients and 29,710 control samples identified by searching PubMed and EMBase databases. Odds ratios (OR) with 95% confidence interval (CI) were applied to assess the association between SNCA rs11931074 polymorphism and PD. Heterogeneity, sensitivity analysis, and publication bias were conducted to measure the robustness of our findings. Using allele, recessive, dominant, and additive models, we did not reveal significant heterogeneity among 33 studies. Significant association of the SNCA rs11931074 polymorphism with PD was observed (T vs. G: OR = 1.36, 95% CI = 1.31–1.42; TT vs. TG + GG: OR = 1.58, 95% CI = 1.46–1.72; TT + TG vs. GG: OR = 1.44, 95% CI = 1.35–1.55; TT vs. GG: OR = 1.87, 95% CI = 1.68–2.09) in the pooled populations. Furthermore, subgroup analyses accounting for ethnicity found similar significant results in both Asian and Caucasian populations. In conclusion, our meta-analysis further indicates that the SNCA rs11931074 polymorphism contributes to PD susceptibility. We believe that our findings will be very useful for future genetic studies on PD.


SNCA rs11931074 Polymorphism Meta-analysis Parkinson’s disease 



We would like to thank Kyuyoung Song for providing the exact number of original genotypes of their study.

Funding information

This work was supported by the National Natural Science Foundation of China (Grant No. 81400950, 81501006).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10072_2018_3538_MOESM1_ESM.docx (22 kb)
Supplementary Table 1 (DOCX 21 kb)
10072_2018_3538_MOESM2_ESM.docx (181 kb)
ESM 1 (DOCX 180 kb)


  1. 1.
    Barnett R (2016) Parkinson’s disease. Lancet (London, England) 387(10015):217. CrossRefGoogle Scholar
  2. 2.
    Cannon JR, Greenamyre JT (2013) Gene-environment interactions in Parkinson’s disease: specific evidence in humans and mammalian models. Neurobiol Dis 57:38–46. CrossRefPubMedGoogle Scholar
  3. 3.
    Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G (2010) Missing pieces in the Parkinson’s disease puzzle. Nat Med 16(6):653–661. CrossRefPubMedGoogle Scholar
  4. 4.
    Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 26(Suppl 1):S1–S58. CrossRefPubMedGoogle Scholar
  5. 5.
    Chung SJ, Armasu SM, Anderson KJ, Biernacka JM, Lesnick TG, Rider DN, Cunningham JM, Ahlskog JE, Frigerio R, Maraganore DM (2013) Genetic susceptibility loci, environmental exposures, and Parkinson’s disease: a case-control study of gene-environment interactions. Parkinsonism Relat Disord 19(6):595–599. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kenborg L, Lassen CF, Ritz B, Schernhammer ES, Hansen J, Gatto NM, Olsen JH (2011) Outdoor work and risk for Parkinson’s disease: a population-based case-control study. Occup Environ Med 68(4):273–278. CrossRefPubMedGoogle Scholar
  7. 7.
    Edwards TL, Scott WK, Almonte C, Burt A, Powell EH, Beecham GW, Wang L, Zuchner S, Konidari I, Wang G, Singer C, Nahab F, Scott B, Stajich JM, Pericak-Vance M, Haines J, Vance JM, Martin ER (2010) Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet 74(2):97–109. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, Kay DM, Doheny KF, Paschall J, Pugh E, Kusel VI, Collura R, Roberts J, Griffith A, Samii A, Scott WK, Nutt J, Factor SA, Payami H (2010) Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet 42(9):781–785. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pankratz N, Wilk JB, Latourelle JC, DeStefano AL, Halter C, Pugh EW, Doheny KF, Gusella JF, Nichols WC, Foroud T, Myers RH, Psg P, GenePd Investigators C, Molecular Genetic L (2009) Genome wide association study for susceptibility genes contributing to familial Parkinson disease. Hum Genet 124(6):593–605. CrossRefPubMedGoogle Scholar
  10. 10.
    Saad M, Lesage S, Saint-Pierre A, Corvol JC, Zelenika D, Lambert JC, Vidailhet M, Mellick GD, Lohmann E, Durif F, Pollak P, Damier P, Tison F, Silburn PA, Tzourio C, Forlani S, Loriot MA, Giroud M, Helmer C, Portet F, Amouyel P, Lathrop M, Elbaz A, Durr A, Martinez M, Brice A, French Parkinson's Disease Genetics Study G (2011) Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson’s disease in the European population. Hum Mol Genet 20(3):615–627. CrossRefPubMedGoogle Scholar
  11. 11.
    Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Kruger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, Steffens M, Okun MS, Racette BA, Cookson MR, Foote KD, Fernandez HH, Traynor BJ, Schreiber S, Arepalli S, Zonozi R, Gwinn K, van der Brug M, Lopez G, Chanock SJ, Schatzkin A, Park Y, Hollenbeck A, Gao J, Huang X, Wood NW, Lorenz D, Deuschl G, Chen H, Riess O, Hardy JA, Singleton AB, Gasser T (2009) Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 41(12):1308–1312. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Simon-Sanchez J, van Hilten JJ, van de Warrenburg B, Post B, Berendse HW, Arepalli S, Hernandez DG, de Bie RM, Velseboer D, Scheffer H, Bloem B, van Dijk KD, Rivadeneira F, Hofman A, Uitterlinden AG, Rizzu P, Bochdanovits Z, Singleton AB, Heutink P (2011) Genome-wide association study confirms extant PD risk loci among the Dutch. Eur J Hum Genet 19(6):655–661. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Consortium UKPsD, Wellcome Trust Case Control C, Spencer CC, Plagnol V, Strange A, Gardner M, Paisan-Ruiz C, Band G, Barker RA, Bellenguez C, Bhatia K, Blackburn H, Blackwell JM, Bramon E, Brown MA, Brown MA, Burn D, Casas JP, Chinnery PF, Clarke CE, Corvin A, Craddock N, Deloukas P, Edkins S, Evans J, Freeman C, Gray E, Hardy J, Hudson G, Hunt S, Jankowski J, Langford C, Lees AJ, Markus HS, Mathew CG, MI MC, Morrison KE, Palmer CN, Pearson JP, Peltonen L, Pirinen M, Plomin R, Potter S, Rautanen A, Sawcer SJ, Su Z, Trembath RC, Viswanathan AC, Williams NW, Morris HR, Donnelly P, Wood NW (2011) Dissection of the genetics of Parkinson’s disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21. Hum Mol Genet 20(2):345–353. CrossRefGoogle Scholar
  14. 14.
    Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, Nakamura Y, Toda T (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41(12):1303–1307. CrossRefPubMedGoogle Scholar
  15. 15.
    Guo JF, Li K, Yu RL, Sun QY, Wang L, Yao LY, Hu YC, Lv ZY, Luo LZ, Shen L, Jiang H, Yan XX, Pan Q, Xia K, Tang BS (2015) Polygenic determinants of Parkinson’s disease in a Chinese population. Neurobiol Aging 36(4):1765 e1761–1765 e1766. CrossRefGoogle Scholar
  16. 16.
    Chen Y, Wei QQ, Ou R, Cao B, Chen X, Zhao B, Guo X, Yang Y, Chen K, Wu Y, Song W, Shang HF (2015) Genetic variants of SNCA are associated with susceptibility to Parkinson’s disease but not amyotrophic lateral sclerosis or multiple system atrophy in a Chinese population. PLoS One 10(7):e0133776. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu-Chou YH, Chen YT, Yeh TH, Chang HC, Weng YH, Lai SC, Huang CL, Chen RS, Huang YZ, Chen CC, Hung J, Chuang WL, Lin WY, Chen CH, Lu CS (2013) Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: a replication study in a Taiwanese cohort. Parkinsonism Relat Disord 19(2):251–255. CrossRefPubMedGoogle Scholar
  18. 18.
    Liu J, Xiao Q, Wang Y, Xu ZM, Wang Y, Yang Q, Wang G, Tan YY, Ma JF, Zhang J, Huang W, Chen SD (2013) Analysis of genome-wide association study-linked loci in Parkinson’s disease of mainland China. Mov Disord 28(13):1892–1895. CrossRefPubMedGoogle Scholar
  19. 19.
    Chang XL, Mao XY, Li HH, Zhang JH, Li NN, Burgunder JM, Peng R, Tan EK (2011) Association of GWAS loci with PD in China. Am J Med Genet B Neuropsychiatr Genet 156b(3):334–339. CrossRefPubMedGoogle Scholar
  20. 20.
    Heckman MG, Elbaz A, Soto-Ortolaza AI, Serie DJ, Aasly JO, Annesi G, Auburger G, Bacon JA, Boczarska-Jedynak M, Bozi M, Brighina L, Chartier-Harlin MC, Dardiotis E, Destee A, Ferrarese C, Ferraris A, Fiske B, Gispert S, Hadjigeorgiou GM, Hattori N, Ioannidis JP, Jasinska-Myga B, Jeon BS, Kim YJ, Klein C, Kruger R, Kyratzi E, Lin CH, Lohmann K, Loriot MA, Lynch T, Mellick GD, Mutez E, Opala G, Park SS, Petrucci S, Quattrone A, Sharma M, Silburn PA, Sohn YH, Stefanis L, Tadic V, Tomiyama H, Uitti RJ, Valente EM, Vassilatis DK, Vilarino-Guell C, White LR, Wirdefeldt K, Wszolek ZK, Wu RM, Xiromerisiou G, Maraganore DM, Farrer MJ, Ross OA, Genetic Epidemiology Of Parkinson's Disease C (2014) Protective effect of LRRK2 p.R1398H on risk of Parkinson’s disease is independent of MAPT and SNCA variants. Neurobiol Aging 35(1):266 e265–266 e214. CrossRefGoogle Scholar
  21. 21.
    Chung SJ, Jung Y, Hong M, Kim MJ, You S, Kim YJ, Kim J, Song K (2013) Alzheimer's disease and Parkinson’s disease genome-wide association study top hits and risk of Parkinson’s disease in Korean population. Neurobiol Aging 34(11):2695 e2691–2695 e2697. CrossRefGoogle Scholar
  22. 22.
    Winkler S, Hagenah J, Lincoln S, Heckman M, Haugarvoll K, Lohmann-Hedrich K, Kostic V, Farrer M, Klein C (2007) alpha-Synuclein and Parkinson disease susceptibility. Neurology 69(18):1745–1750. CrossRefPubMedGoogle Scholar
  23. 23.
    Shahmohammadibeni N, Rahimi-Aliabadi S, Jamshidi J, Emamalizadeh B, Shahmohammadibeni HA, Zare Bidoki A, Akhavan-Niaki H, Eftekhari H, Abdollahi S, Shekari Khaniani M, Shahmohammadibeni M, Fazeli A, Motallebi M, Taghavi S, Ahmadifard A, Shafiei Zarneh AE, Andarva M, Dadkhah T, Khademi E, Alehabib E, Rahimi M, Tafakhori A, Atakhorrami M, Darvish H (2016) The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson’s disease in Iranian population. Neurol Sci 37:731–736. CrossRefPubMedGoogle Scholar
  24. 24.
    Tan EK, Kwok HH, Tan LC, Zhao WT, Prakash KM, Au WL, Pavanni R, Ng YY, Satake W, Zhao Y, Toda T, Liu JJ (2010) Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology 75(6):508–512. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Campelo CLC, Cagni FC, de Siqueira Figueredo D, Oliveira LG Jr, Silva-Neto AB, Macedo PT, Santos JR, Izidio GS, Ribeiro AM, de Andrade TG, de Oliveira Godeiro C Jr, Silva RH (2017) Variants in SNCA gene are associated with Parkinson’s disease risk and cognitive symptoms in a Brazilian sample. Front Aging Neurosci 9:198. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Cookson MR (2005) The biochemistry of Parkinson’s disease. Annu Rev Biochem 74:29–52. CrossRefPubMedGoogle Scholar
  27. 27.
    Miklya I, Pencz N, Hafenscher F, Goltl P (2014) The role of alpha-synuclein in Parkinson’s disease. Neuropsychopharmacol Hung 16(2):77–84PubMedGoogle Scholar
  28. 28.
    Luk KC, Lee VM (2014) Modeling Lewy pathology propagation in Parkinson’s disease. Parkinsonism Relat Disord 20(Suppl 1):S85–S87. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Khalaf O, Fauvet B, Oueslati A, Dikiy I, Mahul-Mellier AL, Ruggeri FS, Mbefo MK, Vercruysse F, Dietler G, Lee SJ, Eliezer D, Lashuel HA (2014) The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity. J Biol Chem 289(32):21856–21876. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bozi M, Papadimitriou D, Antonellou R, Moraitou M, Maniati M, Vassilatis DK, Papageorgiou SG, Leonardos A, Tagaris G, Malamis G, Theofilopoulos D, Kamakari S, Stamboulis E, Hadjigeorgiou GM, Athanassiadou A, Michelakakis H, Papadimitriou A, Gasser T, Stefanis L (2014) Genetic assessment of familial and early-onset Parkinson’s disease in a Greek population. Eur J Neurol 21(7):963–968. CrossRefPubMedGoogle Scholar
  31. 31.
    Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55(2):164–173. CrossRefPubMedGoogle Scholar
  32. 32.
    Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, Levecque C, Larvor L, Andrieux J, Hulihan M, Waucquier N, Defebvre L, Amouyel P, Farrer M, Destee A (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet 364(9440):1167–1169. CrossRefPubMedGoogle Scholar
  33. 33.
    Ibanez P, Bonnet AM, Debarges B, Lohmann E, Tison F, Pollak P, Agid Y, Durr A, Brice A (2004) Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet 364(9440):1169–1171. CrossRefPubMedGoogle Scholar
  34. 34.
    Toffoli M, Dreussi E, Cecchin E, Valente M, Sanvilli N, Montico M, Gagno S, Garziera M, Polano M, Savarese M, Calandra-Buonaura G, Placidi F, Terzaghi M, Toffoli G, Gigli GL (2017) SNCA 3’UTR genetic variants in patients with Parkinson’s disease and REM sleep behavior disorder. Neurol Sci 38(7):1233–1240. CrossRefPubMedGoogle Scholar
  35. 35.
    Venda LL, Cragg SJ, Buchman VL, Wade-Martins R (2010) alpha-Synuclein and dopamine at the crossroads of Parkinson’s disease. Trends Neurosci 33(12):559–568. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    McCarthy JJ, Linnertz C, Saucier L, Burke JR, Hulette CM, Welsh-Bohmer KA, Chiba-Falek O (2011) The effect of SNCA 3′ region on the levels of SNCA-112 splicing variant. Neurogenetics 12(1):59–64. CrossRefPubMedGoogle Scholar
  37. 37.
    Cardo LF, Coto E, de Mena L, Ribacoba R, Mata IF, Menendez M, Moris G, Alvarez V (2014) Alpha-synuclein transcript isoforms in three different brain regions from Parkinson’s disease and healthy subjects in relation to the SNCA rs356165/rs11931074 polymorphisms. Neurosci Lett 562:45–49. CrossRefPubMedGoogle Scholar
  38. 38.
    Hu Y, Tang B, Guo J, Wu X, Sun Q, Shi C, Hu L, Wang C, Wang L, Tan L, Shen L, Yan X, Zhang H (2012) Variant in the 3′ region of SNCA associated with Parkinson’s disease and serum alpha-synuclein levels. J Neurol 259(3):497–504. CrossRefPubMedGoogle Scholar
  39. 39.
    Kang W, Chen W, Yang Q, Zhang L, Zhang L, Wang X, Dong F, Zhao Y, Chen S, Quinn TJ, Zhang J, Chen S, Liu J (2016) Salivary total alpha-synuclein, oligomeric alpha-synuclein and SNCA variants in Parkinson’s disease patients. Sci Rep 6:28143. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Han W, Liu Y, Mi Y, Zhao J, Liu D, Tian Q (2015) Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson’s disease: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 168b(2):123–134. CrossRefPubMedGoogle Scholar

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© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyFirst Affiliated Hospital of China Medical UniversityShenyangChina

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