OBJECTIVE: To classify the patterns of functional decline in @entity1 with sporadic @entity746 ( @entity746 ) and explore the genetic backgrounds that modified these patterns. METHODS: We included 465 @entity1 with @entity4572 in the analysis and clustered the longitudinal functional scores in the registered @entity1 , using a mixture approach of a non-linear mixed-effects model. We conducted a genome-wide analysis of 572   983 single nucleotide polymorphisms (SNPs). We then assessed the association between the clusters of longitudinal functional scores and SNPs. RESULTS: We identified the following four clusters of longitudinal functional decline in the cases: a rapid decline cluster, an intermediate decline cluster, a sigmoidal decline cluster and a moderate decline cluster. We identified seven SNPs associated with the rapid decline cluster, using a recessive model (p=3.47-8.34*10(-8)). The OR for the probabilities of the rapid decline cluster ranged from 5.5 to 5.84. Homozygosity for the minor alleles in the seven SNPs, which constituted a linkage disequilibrium (LD) block, was associated with decreased expression of @entity10484 (encoding @entity10484 , a large sarcomere protein) in the expression quantitative trait loci database of a large-scale Japanese genetic variation database (p=8.6*10(-10)-1.1*10(-7)). @entity10484 expression in immortalised lymphocyte lines was decreased in @entity1 who were homozygous for the minor alleles compared with those who were homozygous for the major alleles (n=19 in each group, p=0.002). CONCLUSIONS: We detected an LD block associated with a rapid functional decline in @entity1 with @entity4572 , which is linked to decreased expression of @entity10484 .

A rapid functional decline type of XXXX is linked to low expression of @entity10484 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity4572 :: ('MESH:C566291', 'Disease') :: ['sporadic ALS'] @entity10484 :: ('7273', 'Gene') :: ['TTN', 'Titin'] @entity746 :: ('MESH:D000690', 'Disease') :: ['ALS', 'amyotrophic lateral sclerosis']
@entity746 :: (MESH:D000690,Disease) :: ['amyotrophic lateral sclerosis']
