PMC:3480684 / 3735-8362 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3480684","sourcedb":"PMC","sourceid":"3480684","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3480684","text":"Methods\n\nStudy subjects\nKorean Association Resource (KARE) study was collected through the Korean Genome Epidemiologic Study project - in total, 10,038 people, 40-69 years old, living in Ansung and Ansan, from 2001-2002. For more information, the study has already been reported [9, 15]. The Health Examinee cohort (HEXA) shared project is a community-based epidemiological cohort of 1,200,000 subjects (aged, 40-69) who were recruited for baseline examination from 2004 to 2009. To share the controls, 4,302 subjects were randomly selected to participate between 2006 and 2007. The BioBank Japan study was approved by the ethical committees in the Institute of Medical Science, the University of Tokyo, and the Center for Genomic Medicine, RIKEN. Subjects for the Health2 cohorts for the replication study were selected from another community-based cohort sample provided by the Health2 study, as described previously [15]. We examined 7,861 selected from the 8,500 participants (aged, 40-69). The students aged 9 and 12 years were recruited from Gwacheon City and Gyeonggi Province between April and June 2010. This study was conducted as part of the Korean Children-Adolescents Study (KoCAS), which has been monitored yearly since their entry into elementary school at age 7 in Gwacheon City or fourth grade at age 10 in Seoul and Gyeonggi Province, Korea. Subjects who were enrolled in a specific diet program or were taking any medications known to affect appetite were excluded from the study. The study protocol was approved by the institutional review board of Seoul-Paik Hospital, Inje University, and the Korea Center for Disease Control and Prevention. Informed consent was obtained from the children's parents.\n\nGenotyping\nKARE samples were genotyped using Affymetrix Genome-Wide Human SNP array 5.0 (Affymetrix, Santa Clara, CA, USA) and processed by Bayesian Robust Linear Modeling using the Mahalanobis Distance (BRLMM) genotyping algorithm [16]. The HEXA shared sample was genotyped using Affymetrix Genome-Wide Human SNP array 6.0 and processed with the Birdseed Genotyping Algorithm [17]. The BioBank Japan study was genotyped using the Illumina Human610-Quad BeadChip (Illumina Inc., San Diego, CA, USA). A childhood obesity study was genotyped using the Illumina Omni1-Quad BeadChip. Individuals were excluded as follows: genotyping call rate, sex inconsistency, heterozygosity, identity-by-state value, and any kinds of tumor. For more information, the study has been reported [15].\nFor the replication study in Health2 (7,861), we performed a genotype assay using the TaqMan reaction for four single nucleotide polymorphisms (SNPs) (rs2074356, rs16940212, rs12708980, rs599839) and the GoldenGate assay (Illumina Inc.) for nine SNPs (rs780092, rs10503669, rs2001945, rs603446, rs12686004, rs11216126, rs12229654, rs519113, rs12654264, rs2738446). To analyze the quality control, we conducted duplicate genotyping using 1-2.5% of samples. For further association analyses, concordance rates were satisfied with duplicates of over 99% and a genotype success rate of over 98%.\n\nSNP imputation\nIn each GWAS data point, imputation analysis was performed using the IMPUTE reference HapMap Asian (Japanese [JPT]/Han Chinese [CHB]) population panel, based on NCBI build 36 and dbSNP build 129. Of these, in each cohort, we dropped SNPs with a posterior probability score \u003c 0.90, high genotype information content (info \u003c 0.5), Hardy-Weinberg equilibrium (HWE) (p \u003c 1 × 10-7), SNP missing rate \u003e 0.1, and minor allele frequency (MAF) \u003c 0.01. In the former analysis, only imputed SNPs that satisfied the genomewide SNP quality control criteria were considered.\n\nAssociation analysis\nIn performing the association tests, SNPs were analyzed with PLINK (http://pngu.mgh.harvard.edu/~purcell/plink/) and SAS version 9.1 (SAS institute Inc., Cary, NC, USA). Individuals who were on lipid-lowering therapy and hypertensive medications were excluded for dyslipidemia-related phenotypes, such as TG, HDL-C, and LDL-C. LDL-C concentrations were calculated with Friedewald's formula [18]. Missing values were assigned for individuals with TG over 400 mg/dL. The dyslipidemia-related phenotypes were tested by multivariate linear regression analysis in an additive genetic model (1-d.f.), including age, sex, and recruitment area as covariates. TG and HDL-C were transformed prior to analysis using natural log transformation to remove skewing. LDL-C was normally distributed, and no transformations were required. A GRS was examined using multivariate linear regression analysis, adjusting for age, sex, and recruitment area.","divisions":[{"label":"Title","span":{"begin":0,"end":7}},{"label":"Section","span":{"begin":9,"end":1722}},{"label":"Title","span":{"begin":9,"end":23}},{"label":"Section","span":{"begin":1724,"end":3095}},{"label":"Title","span":{"begin":1724,"end":1734}},{"label":"Section","span":{"begin":3097,"end":3672}},{"label":"Title","span":{"begin":3097,"end":3111}},{"label":"Title","span":{"begin":3674,"end":3694}}],"tracks":[{"project":"2_test","denotations":[{"id":"23105936-21909109-44845776","span":{"begin":280,"end":281},"obj":"21909109"},{"id":"23105936-19396169-44845777","span":{"begin":283,"end":285},"obj":"19396169"},{"id":"23105936-19396169-44845778","span":{"begin":920,"end":922},"obj":"19396169"},{"id":"23105936-16267090-44845779","span":{"begin":1957,"end":1959},"obj":"16267090"},{"id":"23105936-19117518-44845780","span":{"begin":2102,"end":2104},"obj":"19117518"},{"id":"23105936-19396169-44845781","span":{"begin":2499,"end":2501},"obj":"19396169"},{"id":"23105936-9365406-44845782","span":{"begin":4086,"end":4088},"obj":"9365406"}],"attributes":[{"subj":"23105936-21909109-44845776","pred":"source","obj":"2_test"},{"subj":"23105936-19396169-44845777","pred":"source","obj":"2_test"},{"subj":"23105936-19396169-44845778","pred":"source","obj":"2_test"},{"subj":"23105936-16267090-44845779","pred":"source","obj":"2_test"},{"subj":"23105936-19117518-44845780","pred":"source","obj":"2_test"},{"subj":"23105936-19396169-44845781","pred":"source","obj":"2_test"},{"subj":"23105936-9365406-44845782","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ddec93","default":true}]}]}}