Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study

Kyung Tai Lee, Mi Jeong Byun, Kyung Soo Kang, Eung Woo Park, Seung Hwan Lee, Seoae Cho, Hyo Young Kim, Kyu Won Kim, Tae Heon Lee, Jong Eun Park, Won Cheoul Park, Dong Hyun Shin, Hong Seog Park, Jin Tae Jeon, Bong Hwan Choi, Gul Won Jang, Sang Haeng Choi, Dae Won Kim, Dajeong Lim, Hae Suk ParkMi Rim Park, Jurg Ott, Lawrence B. Schook, Tae Hun Kim, Heebal Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere16356
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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