Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

详细信息    查看全文

• 作者：Lasse Pihlstr&oslash ; m^a ; ^{lasse.pihlstrom@ous-hf.no} ; Gunnar Axelsson^b ; ^c ; ^d ; Kari Anne Bj&oslash ; rnarå ; ^e ; Nil Dizdar^f ; Camilla Fardell^g ; Lars Forsgren^c ; Bjö ; rn Holmberg^h ; Jan Petter Larsenⁱ ; Jan Linder^c ; Hans Nissbrandt^g ; Ole-Bj&oslash ; rn Tysnes^j ; Eilert Ö ; hman^b ; ^c ; ^k ; Espen Dietrichs^a ; ^l ; Mathias Toft^a
• 关键词：Parkinson's disease ; GWAS ; Genetic association study ; Single-nucleotide polymorphism
• 刊名：Neurobiology of Aging
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：34
• 期：6
• 页码：1708.e7-1708.e13
• 全文大小：250 K

文摘

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225?control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.