Linkage and genome-wide association analysis of obesity-related phenotypes: association of weight with the MGAT1 gene.
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.
Johansson
Asa
A
Department of Genetics and Pathology, Rudbeck laboratory, Uppsala University, Uppsala, Sweden.
Marroni
Fabio
F
Hayward
Caroline
C
Franklin
Christopher S
CS
Kirichenko
Anatoly V
AV
Jonasson
Inger
I
Hicks
Andrew A
AA
Vitart
Veronique
V
Isaacs
Aaron
A
Axenovich
Tatiana
T
Campbell
Susan
S
Floyd
Jamie
J
Hastie
Nick
N
Knott
Sara
S
Lauc
Gordan
G
Pichler
Irene
I
Rotim
Kresimir
K
Wild
Sarah H
SH
Zorkoltseva
Irina V
IV
Wilson
James F
JF
Rudan
Igor
I
Campbell
Harry
H
Pattaro
Cristian
C
Pramstaller
Peter
P
Oostra
Ben A
BA
Wright
Alan F
AF
van Duijn
Cornelia M
CM
Aulchenko
Yurii S
YS
Gyllensten
Ulf
U
D000217:Acyltransferases / Q000235:genetics*; D015992:Body Mass Index; D002874:Chromosome Mapping; D004041:Dietary Fats / Q000378:metabolism*; D005060:Europe; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D005810:Multigene Family; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D004041:Dietary Fats; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase