Shi Yao1, Hao Wu1, Jing-Miao Ding1, Zhuo-Xin Wang1, Tahir Ullah1, Shan-Shan Dong1, Hao Chen2, Yan Guo3. 1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China. 2. Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China. chenhaobgl2@xjtu.edu.cn. 3. Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China. guoyan253@xjtu.edu.cn.
Abstract
BACKGROUND: Childhood obesity is one of the most common and costly nutritional problems with high heritability. The genetic mechanism of childhood obesity remains unclear. Here, we conducted a transcriptome-wide association study (TWAS) to identify novel genes for childhood obesity. METHODS: By integrating the GWAS summary of childhood body mass index (BMI), we conducted TWAS analyses with pre-computed gene expression weights in 39 obesity priority tissues. The GWAS summary statistics of childhood BMI were derived from the early growth genetics consortium with 35,668 children from 20 studies. RESULTS: We identified 15 candidate genes for childhood BMI after Bonferroni corrections. The most significant gene, ADCY3, was identified in 13 tissues, including adipose, brain, and blood. Interestingly, eight genes were only identified in the specific tissue, such as FAIM2 in the brain (P = 2.04 × 10-7) and fat mass and obesity-associated gene (FTO) in the muscle (P = 1.93 × 10-8). Compared with the TWAS results of adult BMI, we found that one gene TUBA1B with predominant influence only on childhood BMI in the muscle (P = 1.12 × 10-7). We evaluated the candidate genes by querying public databases and identified 12 genes functionally related to obesity phenotypes, including nine differentially expressed genes during the differentiation of human preadipocyte cells. The remaining genes (FAM150B, KNOP1, and LMBR1L) were regarded as novel candidate genes for childhood BMI. CONCLUSIONS: Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.
BACKGROUND: Childhood obesity is one of the most common and costly nutritional problems with high heritability. The genetic mechanism of childhood obesity remains unclear. Here, we conducted a transcriptome-wide association study (TWAS) to identify novel genes for childhood obesity. METHODS: By integrating the GWAS summary of childhood body mass index (BMI), we conducted TWAS analyses with pre-computed gene expression weights in 39 obesity priority tissues. The GWAS summary statistics of childhood BMI were derived from the early growth genetics consortium with 35,668 children from 20 studies. RESULTS: We identified 15 candidate genes for childhood BMI after Bonferroni corrections. The most significant gene, ADCY3, was identified in 13 tissues, including adipose, brain, and blood. Interestingly, eight genes were only identified in the specific tissue, such as FAIM2 in the brain (P = 2.04 × 10-7) and fat mass and obesity-associated gene (FTO) in the muscle (P = 1.93 × 10-8). Compared with the TWAS results of adult BMI, we found that one gene TUBA1B with predominant influence only on childhood BMI in the muscle (P = 1.12 × 10-7). We evaluated the candidate genes by querying public databases and identified 12 genes functionally related to obesity phenotypes, including nine differentially expressed genes during the differentiation of human preadipocyte cells. The remaining genes (FAM150B, KNOP1, and LMBR1L) were regarded as novel candidate genes for childhood BMI. CONCLUSIONS: Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.
Authors: Jonathan P Bradfield; Suzanne Vogelezang; Janine F Felix; Alessandra Chesi; Øyvind Helgeland; Momoko Horikoshi; Ville Karhunen; Estelle Lowry; Diana L Cousminer; Tarunveer S Ahluwalia; Elisabeth Thiering; Eileen Tai-Hui Boh; Mohammad H Zafarmand; Natalia Vilor-Tejedor; Carol A Wang; Raimo Joro; Zhanghua Chen; William J Gauderman; Niina Pitkänen; Esteban J Parra; Lindsay Fernandez-Rhodes; Akram Alyass; Claire Monnereau; John A Curtin; Christian T Have; Shana E McCormack; Mette Hollensted; Christine Frithioff-Bøjsøe; Adan Valladares-Salgado; Jesus Peralta-Romero; Yik-Ying Teo; Marie Standl; Jaakko T Leinonen; Jens-Christian Holm; Triinu Peters; Jesus Vioque; Martine Vrijheid; Angela Simpson; Adnan Custovic; Marc Vaudel; Mickaël Canouil; Virpi Lindi; Mustafa Atalay; Mika Kähönen; Olli T Raitakari; Barbera D C van Schaik; Robert I Berkowitz; Shelley A Cole; V Saroja Voruganti; Yujie Wang; Heather M Highland; Anthony G Comuzzie; Nancy F Butte; Anne E Justice; Sheila Gahagan; Estela Blanco; Terho Lehtimäki; Timo A Lakka; Johannes Hebebrand; Amélie Bonnefond; Niels Grarup; Philippe Froguel; Leo-Pekka Lyytikäinen; Miguel Cruz; Sayuko Kobes; Robert L Hanson; Babette S Zemel; Anke Hinney; Koon K Teo; David Meyre; Kari E North; Frank D Gilliland; Hans Bisgaard; Mariona Bustamante; Klaus Bonnelykke; Craig E Pennell; Fernando Rivadeneira; André G Uitterlinden; Leslie J Baier; Tanja G M Vrijkotte; Joachim Heinrich; Thorkild I A Sørensen; Seang-Mei Saw; Oluf Pedersen; Torben Hansen; Johan Eriksson; Elisabeth Widén; Mark I McCarthy; Pål R Njølstad; Christine Power; Elina Hyppönen; Sylvain Sebert; Christopher D Brown; Marjo-Riitta Järvelin; Nicholas J Timpson; Stefan Johansson; Hakon Hakonarson; Vincent W V Jaddoe; S F A Grant Journal: Hum Mol Genet Date: 2019-10-01 Impact factor: 6.150
Authors: Janine F Felix; Jonathan P Bradfield; Claire Monnereau; Ralf J P van der Valk; Evie Stergiakouli; Alessandra Chesi; Romy Gaillard; Bjarke Feenstra; Elisabeth Thiering; Eskil Kreiner-Møller; Anubha Mahajan; Niina Pitkänen; Raimo Joro; Alana Cavadino; Ville Huikari; Steve Franks; Maria M Groen-Blokhuis; Diana L Cousminer; Julie A Marsh; Terho Lehtimäki; John A Curtin; Jesus Vioque; Tarunveer S Ahluwalia; Ronny Myhre; Thomas S Price; Natalia Vilor-Tejedor; Loïc Yengo; Niels Grarup; Ioanna Ntalla; Wei Ang; Mustafa Atalay; Hans Bisgaard; Alexandra I Blakemore; Amelie Bonnefond; Lisbeth Carstensen; Johan Eriksson; Claudia Flexeder; Lude Franke; Frank Geller; Mandy Geserick; Anna-Liisa Hartikainen; Claire M A Haworth; Joel N Hirschhorn; Albert Hofman; Jens-Christian Holm; Momoko Horikoshi; Jouke Jan Hottenga; Jinyan Huang; Haja N Kadarmideen; Mika Kähönen; Wieland Kiess; Hanna-Maaria Lakka; Timo A Lakka; Alexandra M Lewin; Liming Liang; Leo-Pekka Lyytikäinen; Baoshan Ma; Per Magnus; Shana E McCormack; George McMahon; Frank D Mentch; Christel M Middeldorp; Clare S Murray; Katja Pahkala; Tune H Pers; Roland Pfäffle; Dirkje S Postma; Christine Power; Angela Simpson; Verena Sengpiel; Carla M T Tiesler; Maties Torrent; André G Uitterlinden; Joyce B van Meurs; Rebecca Vinding; Johannes Waage; Jane Wardle; Eleftheria Zeggini; Babette S Zemel; George V Dedoussis; Oluf Pedersen; Philippe Froguel; Jordi Sunyer; Robert Plomin; Bo Jacobsson; Torben Hansen; Juan R Gonzalez; Adnan Custovic; Olli T Raitakari; Craig E Pennell; Elisabeth Widén; Dorret I Boomsma; Gerard H Koppelman; Sylvain Sebert; Marjo-Riitta Järvelin; Elina Hyppönen; Mark I McCarthy; Virpi Lindi; Niinikoski Harri; Antje Körner; Klaus Bønnelykke; Joachim Heinrich; Mads Melbye; Fernando Rivadeneira; Hakon Hakonarson; Susan M Ring; George Davey Smith; Thorkild I A Sørensen; Nicholas J Timpson; Struan F A Grant; Vincent W V Jaddoe Journal: Hum Mol Genet Date: 2015-11-24 Impact factor: 6.150