title: Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study.
abstract: Obesity represents a major global public health problem that increases the risk for cardiovascular or metabolic disease. The pigs represent an exceptional biomedical model related to energy metabolism and obesity in humans. To pinpoint causal genetic factors for a common form of obesity, we conducted local genomic de novo sequencing, 18.2 Mb, of a porcine QTL region affecting fatness traits, and carried out SNP association studies for backfat thickness and intramuscular fat content in pigs. In order to relate the association studies in pigs to human obesity, we performed a targeted genome wide association study for subcutaneous fat thickness in a cohort population of 8,842 Korean individuals. These combined association studies in human and pig revealed a significant SNP located in a gene family with sequence similarity 73, member A (FAM73A) associated with subscapular skin-fold thickness in humans (rs4121165, GC-corrected p-value  = 0.0000175) and with backfat thickness in pigs (ASGA0029495, p-value  = 0.000031). Our combined association studies also suggest that eight neuronal genes are responsible for subcutaneous fat thickness: NEGR1, SLC44A5, PDE4B, LPHN2, ELTD1, ST6GALNAC3, ST6GALNAC5, and TTLL7. These results provide strong support for a major involvement of the CNS in the genetic predisposition to a common form of obesity.
authors.affiliation: Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea.
authors.forename: Kyung-Tai
authors.initials: KT
authors.lastname: Lee
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Byun
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Kang
authors.forename: Eung-Woo
authors.initials: EW
authors.lastname: Park
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Seoae
authors.initials: S
authors.lastname: Cho
authors.forename: Hyoyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Taeheon
authors.initials: T
authors.lastname: Lee
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Woncheoul
authors.initials: W
authors.lastname: Park
authors.forename: Donghyun
authors.initials: D
authors.lastname: Shin
authors.forename: Hong-Seog
authors.initials: HS
authors.lastname: Park
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Jeon
authors.forename: Bong-Hwan
authors.initials: BH
authors.lastname: Choi
authors.forename: Gul-Won
authors.initials: GW
authors.lastname: Jang
authors.forename: Sang-Haeng
authors.initials: SH
authors.lastname: Choi
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Dajeong
authors.initials: D
authors.lastname: Lim
authors.forename: Hae-Suk
authors.initials: HS
authors.lastname: Park
authors.forename: Mi-Rim
authors.initials: MR
authors.lastname: Park
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schook
authors.forename: Tae-Hun
authors.initials: TH
authors.lastname: Kim
authors.forename: Heebal
authors.initials: H
authors.lastname: Kim
mesh_terms: D050154:Adiposity / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D015331:Cohort Studies; D005260:Female; D005796:Genes / Q000502:physiology; D016678:Genome; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D040641:Quantitative Trait Loci / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D012885:Skinfold Thickness; D050151:Subcutaneous Fat / Q000033:anatomy & histology*; D034421:Sus scrofa / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins