Linkage and Genome-wide Association Analysis of Obesity-related Phenotypes: Association of Weight With the MGAT1 Gene

被引：40

作者：

Johansson, Asa ^{[1
]}

Marroni, Fabio ^{[2
]}

Hayward, Caroline ^{[3
]}

Franklin, Christopher S.

Kirichenko, Anatoly V. ^{[4
]}

Jonasson, Inger ^{[1
]}

Hicks, Andrew A. ^{[2
]}

Vitart, Veronique ^{[3
]}

Isaacs, Aaron ^{[5
]}

Axenovich, Tatiana ^{[4
]}

Campbell, Susan ^{[3
]}

Floyd, Jamie ^{[6
,7
]}

Hastie, Nick ^{[3
]}

Knott, Sara ^{[8
]}

Lauc, Gordan ^{[9
,10
]}

Pichler, Irene ^{[2
]}

Rotim, Kresimir ^{[10
]}

Wild, Sarah H.

Zorkoltseva, Irina V. ^{[4
]}

Wilson, James F.

Rudan, Igor ^{[11
,12
]}

Campbell, Harry

Pattaro, Cristian ^{[2
]}

Pramstaller, Peter ^{[2
,13
]}

Oostra, Ben A. ^{[5
]}

Wright, Alan F. ^{[3
]}

van Duijn, Cornelia M. ^{[5
]}

Aulchenko, Yurii S. ^{[5
]}

Gyllensten, Ulf ^{[1
]}

机构：

[1] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden

[2] EURAC Res, Inst Med Genet, Bolzano, Italy

[3] Western Gen Hosp, Human Genet Unit, MRC, Edinburgh EH4 2XU, Midlothian, Scotland

[4] Russian Acad Sci, Inst Cytol & Genet, Siberian Div, Novosibirsk 630090, Russia

[5] Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat & Clin Genet, Genet Epidemiol Unit, Rotterdam, Netherlands

[6] Univ Edinburgh, Roslin BioCtr, Royal Dick Sch Vet Studies, Edinburgh EH8 9YL, Midlothian, Scotland

[7] Univ Edinburgh, Roslin BioCtr, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland

[8] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH8 9YL, Midlothian, Scotland

[9] Univ Zagreb, Zagreb 41000, Croatia

[10] Univ Osijek, Osijek, Croatia

[11] Univ Hosp Sestre Milosrdnice, Inst Clin Med Res, Zagreb, Croatia

[12] Univ Split, Sch Med, Croatian Ctr Global Hlth, Soltanska, Croatia

[13] Cent Hosp, Dept Neurol, Bolzano, Italy

来源：

OBESITY | 2010年 / 18卷 / 04期

基金：

俄罗斯基础研究基金会; 英国医学研究理事会;

关键词：

ISOLATED DUTCH POPULATION; QUANTITATIVE TRAIT LOCI; RESTING METABOLIC-RATE; BODY-MASS INDEX; SOUTH TYROL; RESPIRATORY QUOTIENT; AFRICAN-AMERICAN; DISEQUILIBRIUM; FAT; VARIANTS;

D O I：

10.1038/oby.2009.359

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：803 / 808

页数：6

共 38 条

[11] The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome [J].

Comuzzie, AG ;

Funahashi, T ;

Sonnenberg, G ;

Martin, LJ ;

Jacob, HJ ;

Black, AEK ;

Maas, D ;

Takahashi, M ;

Kihara, S ;

Tanaka, S ;

Matsuzawa, Y ;

Blangero, J ;

Cohen, D ;

Kissebah, A .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (09) :4321-4325

[12] DNA VARIATION IN THE GENES OF THE NA,K-ADENOSINE TRIPHOSPHATASE AND ITS RELATION WITH RESTING METABOLIC-RATE, RESPIRATORY QUOTIENT, AND BODY-FAT [J].

DERIAZ, O ;

DIONNE, F ;

PERUSSE, L ;

TREMBLAY, A ;

VOHL, MC ;

COTE, G ;

BOUCHARD, C .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :838-843

[13] Dopamine transporter genotype as a risk factor for obesity in African-American smokers [J].

Epstein, LH ;

Jaroni, JL ;

Paluch, RA ;

Leddy, JJ ;

Vahue, HE ;

Hawk, L ;

Wileyto, EP ;

Shields, PG ;

Lerman, C .

OBESITY RESEARCH, 2002, 10 (12) :1232-1240

[14] A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity [J].

Frayling, Timothy M. ;

Timpson, Nicholas J. ;

Weedon, Michael N. ;

Zeggini, Eleftheria ;

Freathy, Rachel M. ;

Lindgren, Cecilia M. ;

Perry, John R. B. ;

Elliott, Katherine S. ;

Lango, Hana ;

Rayner, Nigel W. ;

Shields, Beverley ;

Harries, Lorna W. ;

Barrett, Jeffrey C. ;

Ellard, Sian ;

Groves, Christopher J. ;

Knight, Bridget ;

Patch, Ann-Marie ;

Ness, Andrew R. ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Ring, Susan M. ;

Ben-Shlomo, Yoav ;

Jarvelin, Marjo-Riitta ;

Sovio, Ulla ;

Bennett, Amanda J. ;

Melzer, David ;

Ferrucci, Luigi ;

Loos, Ruth J. F. ;

Barroso, Ines ;

Wareham, Nicholas J. ;

Karpe, Fredrik ;

Owen, Katharine R. ;

Cardon, Lon R. ;

Walker, Mark ;

Hitman, Graham A. ;

Palmer, Colin N. A. ;

Doney, Alex S. F. ;

Morris, Andrew D. ;

Smith, George Davey ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

SCIENCE, 2007, 316 (5826) :889-894

[15] A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10 [J].

Hager, J ;

Dina, C ;

Francke, S ;

Dubois, S ;

Houari, M ;

Vatin, V ;

Vaillant, E ;

Lorentz, N ;

Basdevant, A ;

Clement, K ;

Guy-Grand, B ;

Froguel, P .

NATURE GENETICS, 1998, 20 (03) :304-308

[16] Markov chain Monte Carlo segregation and linkage analysis for oligogenic models [J].

Heath, SC .

AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (03) :748-760

[17] Linkage disequilibrium between microsatellite markers in the Swedish Sami relative to a worldwide selection of populations [J].

Johansson, Å ;

Vavruch-Nilsson, V ;

Edin-Liljegren, A ;

Sjölander, P ;

Gyllensten, U .

HUMAN GENETICS, 2005, 116 (1-2) :105-113

[18] Evaluation of the SNP tagging approach in an independent population sample - array-based SNP discovery in Sami [J].

Johansson, Asa ;

Vavruch-Nilsson, Veronika ;

Cox, David R. ;

Frazer, Kelly A. ;

Gyllensten, Ulf .

HUMAN GENETICS, 2007, 122 (02) :141-150

[19] Linkage and association of the sodium potassium-adenosine triphosphatase (α2 and β1 genes with respiratory quotient and resting metabolic rate in the Quebec Family Study [J].

Katzmarzyk, PT ;

Rankinen, T ;

Pérusse, L ;

Dériaz, O ;

Tremblay, A ;

Borecki, I ;

Rao, DC ;

Bouchard, C .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (06) :2093-2097

[20] Apolipoprotein A-II polymorphism and visceral adiposity in African-American and white women [J].

Lara-Castro, C ;

Hunter, GR ;

Lovejoy, JC ;

Gower, BA ;

Fernández, JR .

OBESITY RESEARCH, 2005, 13 (03) :507-512

← 1 2 3 4 →