Glucocerebrosidase mutations are not a common risk factor for Parkinson disease in North Africa

Nishioka, Kenya; Vilariño‐Güell, Carles; Cobb, Stephanie A.; Kachergus, Jennifer M.; Ross, Owen A.; Wider, Christian; Gibson, Rachel A.; Hentati, Fayçal; Farrer, Matthew J.

doi:10.1016/j.neulet.2009.11.066

Cited by 24 publications

(13 citation statements)

References 29 publications

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“…(Duran, et al, 2013) These racial differences might be derived from the differences of effects of each mutation and other genetic risk factors, which have different distributions due to founder effects. (Lesage, et al, 2011,Nishioka, et al, 2010,Sidransky, et al, 2009) Although racial or regional differences exist for each GBA mutation, our data emphasize that GBA mutations are more strongly associated with FPD, rather than SPD. Li Y et al,Page 11 A recent study reported a relatively high estimated penetrance ratio in GBA carriers, depending on age (7.…”

Section: Discussionmentioning

confidence: 60%

“…(Hruska, et al, 2008,Tsuji, et al, 1987 Some genetic mutations in GBA were characterized as strong risk factors for SPD; however, there are few large studies of GBA mutations in familial PD (FPD). ,Nishioka, et al, 2010,Sidransky, Li Y et al, Page 4 et al, 2009) Co-segregation was previously reported in a small number of families. ) One recent study emphasized an association between GBA mutations and cognitive impairment in PD.…”

Section: Introductionmentioning

confidence: 84%

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Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

Sekine

Funayama

et al. 2014

Neurobiology of Aging

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The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147 Japanese familial PD (FPD) patients from 144 families and 100 unrelated control subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for known Gaucher disease mutations, suggesting that GBA heterozygous mutations are strongly associated with FPD (odds ratio = 22.9, 95% confidence interval = 3.1-171.2). The frequency was significantly higher in autosomal dominant PD (ADPD) compared with autosomal recessive PD. According to clinical assessments, PD patients with GBA mutations exhibited typical manifestations of PD or dementia with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric problems and/or cognitive decline. Interestingly, they also presented with reduced myocardial (123)I-metaiodobenzylguanidine uptake. Our findings suggest that heterozygous GBA mutations are strong risk factors in FPD, especially for autosomal dominant PD. Some patients with GBA heterozygous mutations develop clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body formation, resulting in more severe PD or DLB phenotypes that are inherited in families.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 84%

Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

Sekine

Funayama

et al. 2014

Neurobiology of Aging

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“…Interestingly, the GBA variant rs76763715 (N370S), common in Ashkenazi Jews and one of the most frequently studied GBA variants, did not relate to AAO in our dataset. However, rs75548401 (K26R), first reported as a novel variant in a study of North African PD patients, was significantly associated in our dataset with both PD risk and younger AAO, but not progression [34]. …”

Section: Discussionmentioning

confidence: 99%

Variants in GBA , SNCA , and MAPT influence Parkinson disease risk, age at onset, and progression

Davis

Andruska

Benitez

et al. 2016

Neurobiology of Aging

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Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by Genome-Wide Association Studies (GWAS). The influence that genetic factors confer upon phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used two PD case-control datasets (Washington University and the Parkinson’s Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between SNPs at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression.

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“…Multiple genome-wide association studies (GWAS) for common diseases have been mounted for conditions that are either more prevalent among Ashkenazi Jews (Crohn disease, Parkinson disease) or premised to have less genetic heterogeneity compared with European or European–American populations (breast cancer, diabetes, bipolar disease, schizophrenia). Notably, these GWAS have identified disease-associated variants in the AJ population that were not identified in other populations (Avramopoulos et al 2007; Liu et al 2011; Nishioka et al 2010; Shifman et al 2008). Sequencing strategies hold the possibility of identifying both common and rare variants that affect disease risk as well as response to therapy and development of toxicity.…”

Section: Toward a Personalized Medicine For The Jewish People Based Omentioning

confidence: 99%

The population genetics of the Jewish people

Ostrer

Skorecki

2012

Hum Genet

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Adherents to the Jewish faith have resided in numerous geographic locations over the course of three millennia. Progressively more detailed population genetic analysis carried out independently by multiple research groups over the past two decades has revealed a pattern for the population genetic architecture of contemporary Jews descendant from globally dispersed Diaspora communities. This pattern is consistent with a major, but variable component of shared Near East ancestry, together with variable degrees of admixture and introgression from the corresponding host Diaspora populations. By combining analysis of monoallelic markers with recent genome-wide variation analysis of simple tandem repeats, copy number variations, and single-nucleotide polymorphisms at high density, it has been possible to determine the relative contribution of sex-specific migration and introgression to map founder events and to suggest demographic histories corresponding to western and eastern Diaspora migrations, as well as subsequent microevolutionary events. These patterns have been congruous with the inferences of many, but not of all historians using more traditional tools such as archeology, archival records, linguistics, comparative analysis of religious narrative, liturgy and practices. Importantly, the population genetic architecture of Jews helps to explain the observed patterns of health and disease-relevant mutations and phenotypes which continue to be carefully studied and catalogued, and represent an important resource for human medical genetics research. The current review attempts to provide a succinct update of the more recent developments in a historical and human health context.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-012-1235-6) contains supplementary material, which is available to authorized users.

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Glucocerebrosidase mutations are not a common risk factor for Parkinson disease in North Africa

Abstract: Mutations in the Glucocerebrosidase

Cited by 24 publications

References 29 publications

Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

Variants in GBA , SNCA , and MAPT influence Parkinson disease risk, age at onset, and progression

The population genetics of the Jewish people

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