Genome-wide association study of acute post-surgical pain in humans.
OBJECTIVE
Testing a relatively small genomic region with a few hundred SNPs provides limited information. Genome-wide association studies (GWAS) provide an opportunity to overcome the limitation of candidate gene association studies. Here, we report the results of a GWAS for the responses to an NSAID analgesic.


METHODS
European Americans (60 females and 52 males) undergoing oral surgery were genotyped with Affymetrix 500K SNP assay. Additional SNP genotyping was performed from the gene in linkage disequilibrium with the candidate SNP revealed by the GWAS.


RESULTS
GWAS revealed a candidate SNP (rs2562456) associated with analgesic onset, which is in linkage disequilibrium with a gene encoding a zinc finger protein. Additional SNP genotyping of ZNF429 confirmed the association with analgesic onset in humans (p = 1.8 x 10(-10), degrees of freedom = 103, F = 28.3). We also found candidate loci for the maximum post-operative pain rating (rs17122021, p = 6.9 x 10(-7)) and post-operative pain onset time (rs6693882, p = 2.1 x 10(-6)), however, correcting for multiple comparisons did not sustain these genetic associations.


CONCLUSIONS
GWAS for acute clinical pain followed by additional SNP genotyping of a neighboring gene suggests that genetic variations in or near the loci encoding DNA binding proteins play a role in the individual variations in responses to analgesic drugs.
Kim
Hyungsuk
H
National Institute of Nursing Research, National Institutes of Health, Building 10 CRC 2-1339, 10 Center Drive, Bethesda, MD 20892, USA.
Ramsay
Edward
E
Lee
Hyewon
H
Wahl
Sharon
S
Dionne
Raymond A
RA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D016335:Zinc Fingers / Q000235:genetics
D000700:Analgesics; D004247:DNA