TY - JOUR
T1 - Linkage and genome-wide association analysis of obesity-related phenotypes
T2 - association of weight with the MGAT1 gene
AU - EUROSPAN Consortium
AU - Johansson, Asa
AU - Marroni, Fabio
AU - Hayward, Caroline
AU - Franklin, Christopher S
AU - Kirichenko, Anatoly V
AU - Jonasson, Inger
AU - Hicks, Andrew A
AU - Vitart, Veronique
AU - Isaacs, Aaron
AU - Axenovich, Tatiana
AU - Campbell, Susan
AU - Floyd, Jamie
AU - Hastie, Nick
AU - Knott, Sara
AU - Lauc, Gordan
AU - Pichler, Irene
AU - Rotim, Kresimir
AU - Wild, Sarah H
AU - Zorkoltseva, Irina V
AU - Wilson, James F
AU - Rudan, Igor
AU - Campbell, Harry
AU - Pattaro, Cristian
AU - Pramstaller, Peter
AU - Oostra, Ben A
AU - Wright, Alan F
AU - van Duijn, Cornelia M
AU - Aulchenko, Yurii S
AU - Gyllensten, Ulf
PY - 2012/9/6
Y1 - 2012/9/6
N2 - 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 x 10(-7), Bonferroni-adjusted P <0.05) one single-nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 x 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.
AB - 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 x 10(-7), Bonferroni-adjusted P <0.05) one single-nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 x 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.
U2 - 10.1038/oby.2009.359
DO - 10.1038/oby.2009.359
M3 - Article
C2 - 19851299
SN - 1930-7381
VL - 18
SP - 803
EP - 808
JO - Obesity
JF - Obesity
IS - 4
ER -