A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits.
To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter approximately 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.
Cho
Yoon Shin
YS
Center for Genome Science, National Institute of Health, Seoul, Korea.
Go
Min Jin
MJ
Kim
Young Jin
YJ
Heo
Jee Yeon
JY
Oh
Ji Hee
JH
Ban
Hyo-Jeong
HJ
Yoon
Dankyu
D
Lee
Mi Hee
MH
Kim
Dong-Joon
DJ
Park
Miey
M
Cha
Seung-Hun
SH
Kim
Jun-Woo
JW
Han
Bok-Ghee
BG
Min
Haesook
H
Ahn
Younjhin
Y
Park
Man Suk
MS
Han
Hye Ree
HR
Jang
Hye-Yoon
HY
Cho
Eun Young
EY
Lee
Jong-Eun
JE
Cho
Nam H
NH
Shin
Chol
C
Park
Taesung
T
Park
Ji Wan
JW
Lee
Jong-Keuk
JK
Cardon
Lon
L
Clarke
Geraldine
G
McCarthy
Mark I
MI
Lee
Jong-Young
JY
Lee
Jong-Koo
JK
Oh
Bermseok
B
Kim
Hyung-Lae
HL
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D049629:Waist-Hip Ratio