Table 2.

—Summary of Sleep Disorders With Alleles or Loci That Have Been Associated on the Basis of Candidate Gene, Linkage, or Genome-Wide Association Studies

Sleep Disorder	Associated Gene, Loci, SNP	Comments
Narcolepsy/cataplexy	DQB1 and DQA1; primary allele DQB1*0602	HLA class II allele; effect observed across several ethnic groups; high prevalence (90%) in narcolepsy with cataplexy
Narcolepsy/cataplexy	T-cell receptor α	Based on GWAS; identified across several ethnic groups independently; T-cell receptor on lymphocytes interacts with HLA class I and II antigens, including DQB1*0602 allele
RLS/PLMS	RLS1	Identified in familial linkage studies across several nationalities; complex transmission, but often autosomal dominant, with incomplete penetrance; no association with dopamine system or iron metabolism documented
	RLS2
	RLS3
	RLS4
	RLS5
RLS/PLMS	MEIS1	Based on GWAS; replicated in several studies; MEIS1 associated with motor neuron development
RLS/PLMS	BTBD9	Based on GWAS; associated with PLMS without RLS; allele also associated with reduced ferritin levels
RLS/PLMS	MAP2K5/SKOR1 (LBXCOR1)	Based on GWAS; gene associated with development of dorsal-horn sensory pathways
RLS/PLMS	PTPRD	Based on GWAS; two SNPs involved with neuronal development
Familial advanced sleep phase syndrome	HPER2	Autosomal dominant transmission; identified through candidate gene sequencing
Fatal familial insomnia	Single point mutation in prion gene	Point mutation at position 178 of prion protein gene combined with point mutation at codon 129

GWAS = genome-wide association study; HLA = human leukocyte antigen; PLMS = periodic limb movements in sleep; RLS = restless legs syndrome; SNP = single nucleotide polymorphism.