Genome-wide association of serum bilirubin levels in Korean population.
A large-scale, genome-wide association study was performed to identify genetic variations influencing serum bilirubin levels using 8841 Korean individuals. Significant associations were observed at UGT1A1 (rs11891311, P = 4.78 x 10(-148)) and SLCO1B3 (rs2417940, P = 1.03 x 10(-17)), which are two previously identified loci. The two single-nucleotide polymorphisms (SNPs) were replicated (rs11891311, P = 3.18 x 10(-15)) or marginally significant (rs2417940, P = 8.56 x 10(-4)) in an independent cohort of 1096 individuals. In a conditional analysis adjusted for the top UGT1A1 variant (rs11891311), another variant in UGT1A1 (rs4148323, P = 1.22 x 10(-121)) remained significant; this suggests that in UGT1A1 at least two independent genetic variations influence the bilirubin levels in the Korean population. The protein coding variant rs4148323, which is monomorphic in European-derived populations, may be specifically associated with serum bilirubin levels in Asians (P = 2.56 x 10(-70)). The SLCO1B3 variant (rs2417940, P = 1.67 x 10(-18)) remained significant in a conditional analysis for the top UGT1A1 variant. Interestingly, there were significant differences in the associated variations of SLCO1B3 between Koreans and European-derived populations. While the variant rs2417940 at intron 7 of SLCO1B3 was more significantly associated in Koreans, variants rs17680137 (P = 0.584) and rs2117032 (P = 2.76 x 10(-5)), two of the top-ranked SNPs in European-derived populations, did not reach the genome-wide significance level. Also, variants in SLCO1B1 did not reach genome-wide significance in Koreans. Our result supports the idea that there are considerable ethnic differences in genetic association of bilirubin levels between Koreans and European-derived populations.
Kang
Tae-Wook
TW
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea.
Kim
Hee-Jin
HJ
Ju
Hyoungseok
H
Kim
Jeong-Hwan
JH
Jeon
Yeo-Jin
YJ
Lee
Han-Chul
HC
Kim
Ka-Kyung
KK
Kim
Jong-Won
JW
Lee
Siwoo
S
Kim
Jong Yeol
JY
Kim
Seon-Young
SY
Kim
Yong Sung
YS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001663:Bilirubin / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D044465:White People / Q000235:genetics; D055815:Young Adult; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D029362:Organic Anion Transporters, Sodium-Independent; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000099148:UGT1A1 Enzyme; C421209:SLCO1B3 protein, human