| Literature DB >> 31504550 |
Jonathan P Bradfield1,2, Suzanne Vogelezang3,4,5, Janine F Felix3,4,5, Alessandra Chesi6,7, Øyvind Helgeland8,9, Momoko Horikoshi10,11,12, Ville Karhunen13, Estelle Lowry14, Diana L Cousminer6,7,15, Tarunveer S Ahluwalia16,17,18, Elisabeth Thiering19,20, Eileen Tai-Hui Boh21, Mohammad H Zafarmand22,23, Natalia Vilor-Tejedor4,24,25,26,27, Carol A Wang28, Raimo Joro29, Zhanghua Chen30, William J Gauderman30, Niina Pitkänen31,32, Esteban J Parra33, Lindsay Fernandez-Rhodes34,35, Akram Alyass36, Claire Monnereau3,4,5, John A Curtin37, Christian T Have18, Shana E McCormack38,39, Mette Hollensted18, Christine Frithioff-Bøjsøe18,40, Adan Valladares-Salgado41, Jesus Peralta-Romero41, Yik-Ying Teo21,42,43,44,45, Marie Standl19, Jaakko T Leinonen46, Jens-Christian Holm18,40,47, Triinu Peters48, Jesus Vioque25,49,50, Martine Vrijheid51,24,25, Angela Simpson37, Adnan Custovic52, Marc Vaudel8, Mickaël Canouil53, Virpi Lindi54, Mustafa Atalay29, Mika Kähönen55,56, Olli T Raitakari31,32,57, Barbera D C van Schaik23, Robert I Berkowitz58, Shelley A Cole59, V Saroja Voruganti60, Yujie Wang61, Heather M Highland61, Anthony G Comuzzie62, Nancy F Butte63, Anne E Justice61,64, Sheila Gahagan65, Estela Blanco65, Terho Lehtimäki66,67, Timo A Lakka29,68,69, Johannes Hebebrand48, Amélie Bonnefond53,70, Niels Grarup18, Philippe Froguel53,70, Leo-Pekka Lyytikäinen66,67,71, Miguel Cruz41, Sayuko Kobes72, Robert L Hanson72, Babette S Zemel38,73, Anke Hinney48, Koon K Teo36,74, David Meyre36,75, Kari E North61,76, Frank D Gilliland30, Hans Bisgaard16, Mariona Bustamante51,24,25, Klaus Bonnelykke16, Craig E Pennell28, Fernando Rivadeneira3,4,77, André G Uitterlinden4,77, Leslie J Baier72, Tanja G M Vrijkotte22, Joachim Heinrich19,78,79, Thorkild I A Sørensen18,80,81, Seang-Mei Saw21,82, Oluf Pedersen18, Torben Hansen18, Johan Eriksson83,84,85, Elisabeth Widén46, Mark I McCarthy10,11,86, Pål R Njølstad8,87, Christine Power88, Elina Hyppönen88,89,90, Sylvain Sebert14,91,92, Christopher D Brown93, Marjo-Riitta Järvelin13,14,91,94,95, Nicholas J Timpson81, Stefan Johansson8,96, Hakon Hakonarson1,97, Vincent W V Jaddoe3,4,5, S F A Grant.
Abstract
Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.Entities:
Mesh：
Year: 2019 PMID： 31504550 PMCID： PMC6859434 DOI： 10.1093/hmg/ddz161
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150