title: Whole-exome sequencing study reveals common copy number variants in protocadherin genes associated with childhood obesity in Koreans.
abstract: Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10-4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher's combined P-value=3.76 × 10-5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Moon
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: M Y
authors.initials: MY
authors.lastname: Hwang
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: H B
authors.initials: HB
authors.lastname: Jang
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: S I
authors.initials: SI
authors.lastname: Park
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.affiliation: Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: B-J
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D063766:Pediatric Obesity / Q000235:genetics*; D015203:Reproducibility of Results; D056910:Republic of Korea; D000073359:Exome Sequencing
chemical_list: D015820:Cadherins