Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study |
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Authors: | Lee Kyung-Tai Byun Mi-Jeong Kang Kyung-Soo Park Eung-Woo Lee Seung-Hwan Cho Seoae Kim Hyoyoung Kim Kyu-Won Lee Taeheon Park Jong-Eun Park Woncheoul Shin Donghyun Park Hong-Seog Jeon Jin-Tae Choi Bong-Hwan Jang Gul-Won Choi Sang-Haeng Kim Dae-Won Lim Dajeong Park Hae-Suk Park Mi-Rim Ott Jurg Schook Lawrence B Kim Tae-Hun Kim Heebal |
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Institution: | Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea. |
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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. |
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