Linkage and Genome‐wide Association Analysis of Obesity‐related Phenotypes: Association of Weight With the MGAT1 Gene |
| |
| Authors: | Åsa Johansson Fabio Marroni Caroline Hayward Christopher S Franklin Anatoly V Kirichenko Inger Jonasson Andrew A Hicks Veronique Vitart Aaron Isaacs Tatiana Axenovich Susan Campbell Jamie Floyd Nick Hastie Sara Knott Gordan Lauc Irene Pichler Kresimir Rotim Sarah H Wild Irina V Zorkoltseva James F Wilson Igor Rudan Harry Campbell Cristian Pattaro Peter Pramstaller Ben A Oostra Alan F Wright Cornelia M van Duijn Yurii S Aulchenko Ulf Gyllensten EUROSPAN Consortium |
| |
| Institution: | 1. Department of Genetics and Pathology, Rudbeck laboratory, Uppsala University, Uppsala, Sweden;2. Institute of Genetic Medicine, EURAC research, Viale Druso 1, Bolzano, Italy;3. Medical Research Council, Human Genetics Unit, Western General Hospital, Edinburgh, UK;4. Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, UK;5. Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia;6. Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics and Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands;7. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin BioCentre, Midlothian, UK;8. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK;9. University of Zagreb, Zagreb, Croatia;10. University of Osijek, Osijek, Croatia;11. Institute for Clinical Medical Research, University Hospital “Sestre Milosrdnice”, Zagreb, Croatia;12. Croatian Centre for Global Health, University of Split Medical School, Soltanska, Croatia;13. Department of Neurology, Central Hospital, Bolzano, Italy |
| |
| Abstract: | As major risk‐factors for diabetes and cardiovascular diseases, the genetic contribution to obesity‐related traits has been of interest for decades. Recently, a limited number of common genetic variants, which have replicated in different populations, have been identified. One approach to increase the statistical power in genetic mapping studies is to focus on populations with increased levels of linkage disequilibrium (LD) and reduced genetic diversity. We have performed joint linkage and genome‐wide association analyses for weight and BMI in 3,448 (linkage) and 3,925 (association) partly overlapping healthy individuals from five European populations. A total of four chromosomal regions (two for weight and two for BMI) showed suggestive linkage (lod >2.69) either in one of the populations or in the joint data. At the genome‐wide level (nominal P < 1.6 × 10?7, Bonferroni‐adjusted P < 0.05) one single‐nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 × 10?8) was associated with weight, whereas none with BMI. The SNP associated with weight is located close to MGAT1. The monoacylglycerol acyltransferase (MGAT) enzyme family is known to be involved in dietary fat absorption. There was no overlap between the linkage regions and the associated SNPs. Our results show that genetic effects influencing weight and BMI are shared across diverse European populations, even though some of these populations have experienced recent population bottlenecks and/or been affected by genetic drift. The analysis enabled us to identify a new candidate gene, MGAT1, associated with weight in women. |
| |
| Keywords: | |
|
|
