| Literature DB >> 27680694 |
Momoko Horikoshi1,2, Robin N Beaumont3, Felix R Day4, Nicole M Warrington5,6, Marjolein N Kooijman7,8,9, Juan Fernandez-Tajes1, Bjarke Feenstra10, Natalie R van Zuydam1,2, Kyle J Gaulton1,11, Niels Grarup12, Jonathan P Bradfield13, David P Strachan14, Ruifang Li-Gao15, Tarunveer S Ahluwalia12,16,17, Eskil Kreiner16, Rico Rueedi18,19, Leo-Pekka Lyytikäinen20,21, Diana L Cousminer22,23,24, Ying Wu25, Elisabeth Thiering26,27, Carol A Wang6, Christian T Have12, Jouke-Jan Hottenga28, Natalia Vilor-Tejedor29,30,31, Peter K Joshi32, Eileen Tai Hui Boh33, Ioanna Ntalla34,35, Niina Pitkänen36, Anubha Mahajan1, Elisabeth M van Leeuwen8, Raimo Joro37, Vasiliki Lagou1,38,39, Michael Nodzenski40, Louise A Diver41, Krina T Zondervan1,42, Mariona Bustamante29,30,31,43, Pedro Marques-Vidal44, Josep M Mercader45, Amanda J Bennett2, Nilufer Rahmioglu1, Dale R Nyholt46, Ronald Ching Wan Ma47,48,49, Claudia Ha Ting Tam47, Wing Hung Tam50, Santhi K Ganesh51, Frank Ja van Rooij8, Samuel E Jones3, Po-Ru Loh52,53, Katherine S Ruth3, Marcus A Tuke3, Jessica Tyrrell3,54, Andrew R Wood3, Hanieh Yaghootkar3, Denise M Scholtens40, Lavinia Paternoster55,56, Inga Prokopenko1,57, Peter Kovacs58, Mustafa Atalay37, Sara M Willems8, Kalliope Panoutsopoulou59, Xu Wang33, Lisbeth Carstensen10, Frank Geller10, Katharina E Schraut32, Mario Murcia31,60, Catharina Em van Beijsterveldt28, Gonneke Willemsen28, Emil V R Appel12, Cilius E Fonvig12,61, Caecilie Trier12,61, Carla Mt Tiesler26,27, Marie Standl26, Zoltán Kutalik19,62, Sílvia Bonas-Guarch45, David M Hougaard63,64, Friman Sánchez45,65, David Torrents45,66, Johannes Waage16, Mads V Hollegaard63,64, Hugoline G de Haan15, Frits R Rosendaal15, Carolina Medina-Gomez7,8,67, Susan M Ring55,56, Gibran Hemani55,56, George McMahon56, Neil R Robertson1,2, Christopher J Groves2, Claudia Langenberg4, Jian'an Luan4, Robert A Scott4, Jing Hua Zhao4, Frank D Mentch13, Scott M MacKenzie41, Rebecca M Reynolds68, William L Lowe69, Anke Tönjes70, Michael Stumvoll58,70, Virpi Lindi37, Timo A Lakka37,71,72, Cornelia M van Duijn8, Wieland Kiess73, Antje Körner58,73, Thorkild Ia Sørensen55,56,74,75, Harri Niinikoski76,77, Katja Pahkala36,78, Olli T Raitakari36,79, Eleftheria Zeggini59, George V Dedoussis35, Yik-Ying Teo33,80,81, Seang-Mei Saw33,82, Mads Melbye10,83,84, Harry Campbell32, James F Wilson32,85, Martine Vrijheid29,30,31, Eco Jcn de Geus28,86, Dorret I Boomsma28, Haja N Kadarmideen87, Jens-Christian Holm12,61, Torben Hansen12, Sylvain Sebert88,89, Andrew T Hattersley3, Lawrence J Beilin90, John P Newnham6, Craig E Pennell6, Joachim Heinrich26,91, Linda S Adair92, Judith B Borja93,94, Karen L Mohlke25, Johan G Eriksson95,96,97, Elisabeth E Widén22, Mika Kähönen98,99, Jorma S Viikari100,101, Terho Lehtimäki20,21, Peter Vollenweider44, Klaus Bønnelykke16, Hans Bisgaard16, Dennis O Mook-Kanamori15,102,103, Albert Hofman7,8, Fernando Rivadeneira7,8,67, André G Uitterlinden7,8,67, Charlotta Pisinger104, Oluf Pedersen12, Christine Power105, Elina Hyppönen105,106,107, Nicholas J Wareham4, Hakon Hakonarson13,23,108, Eleanor Davies41, Brian R Walker68, Vincent Wv Jaddoe7,8,9, Marjo-Riitta Jarvelin88,89,109,110, Struan Fa Grant13,23,108,111, Allan A Vaag83,112, Debbie A Lawlor55,56, Timothy M Frayling3, George Davey Smith55,56, Andrew P Morris1,113,114, Ken K Ong4,115, Janine F Felix7,8,9, Nicholas J Timpson55,56, John Rb Perry4, David M Evans5,55,56, Mark I McCarthy1,2,116, Rachel M Freathy3,55.
Abstract
Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10-13), T2D (Rg = -0.27, P = 1.1 × 10-6) and coronary artery disease (Rg = -0.30, P = 6.5 × 10-9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27680694 PMCID： PMC5164934 DOI： 10.1038/nature19806
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962