title: A nonsynonymous SNP in BANK1 is associated with serum LDL cholesterol levels in three Korean populations.
abstract: Serum levels of lipids, such as cholesterol and triglycerides, are heritable risk factors for cardiovascular disease and targets for therapeutic intervention. Because previous genome-wide association studies (GWASs) did not target functional genetic variants, we employed an alternate approach using nonsynonymous single-nucleotide polymorphisms (SNPs) to identify functional genetic variants associated with the regulation of serum lipid levels. We selected 3667 healthy individuals from a rural community-based cohort (CAVAS; Cardio Vascular disease Association Study) of the Korean Genome and Epidemiology Study project. We analyzed demographic and lifestyle information, lipid measurements and genotypes using the Illumina-1M SNP chip. For genotyping, we isolated 11 558 nonsynonymous SNPs and conducted a linear regression analysis with four lipid traits (total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterols and triglycerides). Significantly associated SNPs were validated in two independent Korean populations, Korean Association Resource (KARE) (n=4116) and Health Examinee (HEXA) (n=2178). Of the 11 558 SNPs, one SNP (rs3733197) from the CAVAS was significantly associated with serum LDL cholesterols (beta±s.e.=4.67±0.94, P-value=1.0 × 10(-6 and) Bonferroni corrected P-value=0.012). The replication results of HEXA and KARE were beta±s.e.=2.88±1.12, P-value=0.016 and beta±s.e.=1.26±0.97, P-value=0.196, respectively. An overall meta-analysis of the three data sets revealed beta=2.98±0.57, P-value=6.19 × 10(-7). The rs3733197 is located in the coding region of BANK1 (B-cell scaffold protein with ankyrin repeats 1), and the minor allele (A) resulted in the replacement of the Alanine at position 383 with Threonine.
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Cheongju-si, Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Hong
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Cheongju-si, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lyu
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Cheongju-si, Korea.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Cheongju-si, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Cheongju-si, Korea.
authors.forename: Yeonjung
authors.initials: Y
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D008078:Cholesterol, LDL; D008565:Membrane Proteins; D014280:Triglycerides