Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
W. van Rheenen et al., Nature Genetics, 2016

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom 
imputation reference panel from whole genome- sequenced ALS patients and matched controls (N = 1,861). Through imputation and 
mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent 
replication cohort, we fine mapped a novel locus on chromosome 21 and identified C21orf2 as an ALS risk gene. In addition, we identified 
MOBP and SCFD1 as novel associated risk loci. We established evidence for ALS being a complex genetic trait with a polygenic architecture. 
Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low frequency (1 to 10%) variants. 
This study motivates the interrogation of larger sample sizes with full genome coverage to identify rare causal variants that underpin ALS risk.

COLUMN headings 

DISCOVERY FILE (space-delimited):

chr snp bp a1 a2 freq b se p

META-ANALYSIS FILE (tab-delimited:

chr	snp	bp	a1	a2	freq	b	se	p	direction	het_I2	het_Chi2	het_p	cases	controls


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