Frontotemporal lobar degeneration genome wide association study replication confirms a risk locus shared with amyotrophic lateral sclerosis.
Frontotemporal lobar degeneration (FTLD) is a common cause of dementia especially in patients under the age of 65. FTLD has a high incidence of heritability with as many as 40% of patients reporting a family history of disease. Recently, the first genome wide association study was performed using only FTLD patients with a pathologically confirmed TDP-43 pathology. Genome wide significance was detected for a single gene (TMEM106B) on chromosome 7, though several other loci on chromosomes 1, 8, 9, 10 and 11 reached nominal significance. Here we have undertaken an attempt to replicate the association of these loci in FTLD cohorts of British origin. We failed to detect any association of TMEM106B in the Manchester or London cohort either when analyzed individually or when combined. Genotyping of the Manchester cohort failed to replicate any of the loci on chromosome 1, 8 and 10 but did detect association of the single SNP (rs2015747) on chromosome 11. Association was also observed in the London cohort but in the opposite direction. Combining the 2 datasets yielded no association. Analysis of the chromosome 9 locus, revealed strong association in the London FTLD cohort and the Manchester FTLD+ALS cases. These data confirm that FTLD and amyotrophic lateral sclerosis (ALS) share a common genetic risk factor on chromosome 9p.
Neurodegeneration and Mental Health Research Group, Faculty of Human and Medical Sciences, University of Manchester, AV, Hill Building, Oxford Road, Manchester, M13 9PT, UK.
Sara
S
Rollinson
Simon
S
Mead
Julie
J
Snowden
Anna
A
Richardson
Jonathan
J
Rohrer
Nicola
N
Halliwell
Suzanne
S
Usher
David
D
Neary
David
D
Mann
John
J
Hardy
Stuart
S
Pickering-Brown
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C556915:TMEM106B protein, human