Adiponectin concentrations: a genome-wide association study.
Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.
Jee
Sun Ha
SH
Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea. jsunha@yuhs.ac
Sull
Jae Woong
JW
Lee
Jong-Eun
JE
Shin
Chol
C
Park
Jongkeun
J
Kimm
Heejin
H
Cho
Eun-Young
EY
Shin
Eun-Soon
ES
Yun
Ji Eun
JE
Park
Ji Wan
JW
Kim
Sang Yeun
SY
Lee
Sun Ju
SJ
Jee
Eun Jung
EJ
Baik
Inkyung
I
Kao
Linda
L
Yoon
Sungjoo Kim
SK
Jang
Yangsoo
Y
Beaty
Terri H
TH
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure; D015992:Body Mass Index; D015820:Cadherins / Q000235:genetics*; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA
D052242:Adiponectin; D015820:Cadherins; D017931:DNA Primers; C099972:H-cadherin; D002784:Cholesterol