Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.
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PMID:A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis. 1919 27

A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
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PMID:Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis. 1992 38

DPP6 and FGGY genes have been recently associated with an increased susceptibility for sporadic amyotrophic lateral sclerosis. Here, we evaluated the role of these genes in ALS pathogenesis by undertaking a sequence analysis of a cohort of 190 ALS patients from France and Quebec. We did not observe any evidence that mutations in DPP6 and FGGY genes are involved in ALS. Our data indicate that mutations in these genes are unlikely to be a common cause of ALS in the French and French Canadian populations.
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PMID:Analysis of DPP6 and FGGY as candidate genes for amyotrophic lateral sclerosis. 2000 89

The single-nucleotide polymorphisms (SNPs) rs6700125 and rs6690993 in FGGY (FLJ10986) were recently reported to be a susceptibility factor for sporadic amyotrophic lateral sclerosis (SALS) in Caucasian populations in genome-wide association studies. However, no such association was observed in other independent genome-wide association studies or replication studies in a European cohort or 2 small sample sizes of Chinese patients. We performed a large case-control study in a cohort consisting of 963 SALS cases and 1039 control subjects to examine the association between the 2 reported SNPs in FGGY and amyotrophic lateral sclerosisin Chinese patients. Our results did not find the SNP rs6690993 in FGGY is associated with Chinese SALS and cannot confirm that this FGGY SNP modulates the risk for SALS in the Chinese population.
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PMID:Single-nucleotide polymorphism rs6690993 in FGGY is not associated with amyotrophic lateral sclerosisin a large Chinese cohort. 2443 56