Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes.
Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes.
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在研究中，在Indig2和PFKP中的常见变体与肥胖症中基于全基因组的相关性的不复制在18,014个DANES的研究中。
DOI：
10.1371/journal.pone.0002872
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发表时间：
2008-08-06
期刊：
影响因子：
3.7
通讯作者：
Hansen T
中科院分区：
文献类型：
--
作者：
Andreasen CH;Mogensen MS;Borch-Johnsen K;Sandbaek A;Lauritzen T;Sørensen TI;Hansen L;Almind K;Jørgensen T;Pedersen O;Hansen T
INSIG2 rs7566605 和 PFKP rs6602024 多态性已在全基因组关联 (GWA) 研究中被确定为肥胖基因变异。然而，这两种变体的复制都是矛盾的。本研究的目的是通过病例对照研究和肥胖相关数量性状分析来验证这些肥胖关联。此外，由于环境和遗传因素可能会调节遗传变异的影响，因此我们希望进行此类相互作用分析。我们重点关注身体活动作为环境风险因素，GWA 将 FTO (rs9939609) 和近 MC4R (rs17782313) 附近的肥胖变异确定为遗传风险因素。这四种变异在一个组合研究样本中进行了基因分型，该样本包括总共 18,014 名受试者，这些受试者来自基于人群的 Inter99 队列 (n = 6,514)、ADDITION 筛查队列 (n = 8,662)、基于人群的研究样本 (n = 680) 和 2 型糖尿病患者组(n = 2,158) 来自 Steno 糖尿病中心。 INSIG2 rs7566605 或 PFKP rs6602024 变体均未显示与超重、肥胖或肥胖相关测量值的关联。然而，观察到 INSIG2 rs7566605 变异与自我报告的体力活动水平之间存在相互作用 (p Int = 0.004)。当比较身体被动的纯合 C 等位基因携带者与身体被动的 G 等位基因携带者时，发现 BMI 差异为 0.53 (SE 0.42) kg/m2。没有观察到两个变体与 FTO rs9939609 和 MC4R rs17782313 之间的相互作用。 INSIG2 rs7566605 和 PFKP rs6602024 多态性在丹麦人群常见肥胖形式的发展中没有发挥明显作用。然而，如果重复的话，INSIG2 rs7566605 可能会影响 BMI 水平和体力活动水平。
The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors. The four variants were genotyped in a combined study sample comprising a total of 18,014 subject ascertained from, the population-based Inter99 cohort (n = 6,514), the ADDITION screening cohort (n = 8,662), a population-based study sample (n = 680) and a type 2 diabetic patient group (n = 2,158) from Steno Diabetes Center. No association with overweight, obesity or obesity-related measures was shown for either the INSIG2 rs7566605 or the PFKP rs6602024 variants. However, an interaction between the INSIG2 rs7566605 variant and the level of self-reported physical activity (p Int = 0.004) was observed. A BMI difference of 0.53 (SE 0.42) kg/m2 was found when comparing physically passive homozygous C-allele carriers with physically passive G-allele carriers. No interactions between the two variants and FTO rs9939609 and MC4R rs17782313 were observed. The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. However, if replicated, the INSIG2 rs7566605 may influence the level of BMI in combination with the level of physical activity.
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影响因子：
10.5
作者：
Kim, JB;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
9.8
作者：
BELFIORE, F;BORZI, V;RABUAZZO, AM
通讯作者：
RABUAZZO, AM
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
30.8
作者：
Loos, Ruth J. F.;Lindgren, Cecilia M.;Li, Shengxu;Wheeler, Eleanor;Zhao, Jing Hua;Prokopenko, Inga;Inouye, Michael;Freathy, Rachel M.;Attwood, Antony P.;Beckmann, Jacques S.;Berndt, Sonja I.;Bergmann, Sven;Bennett, Amanda J.;Bingham, Sheila A.;Bochud, Murielle;Brown, Morris;Cauchi, Stephane;Connell, John M.;Cooper, Cyrus;Smith, George Davey;Day, Ian;Dina, Christian;De, Subhajyoti;Dermitzakis, Emmanouil T.;Doney, Alex S. F.;Elliott, Katherine S.;Elliott, Paul;Evans, David M.;Farooqi, I. Sadaf;Froguel, Philippe;Ghori, Jilur;Groves, Christopher J.;Gwilliam, Rhian;Hadley, David;Hall, Alistair S.;Hattersley, Andrew T.;Hebebrand, Johannes;Heid, Iris M.;Herrera, Blanca;Hinney, Anke;Hunt, Sarah E.;Jarvelin, Marjo-Riitta;Johnson, Toby;Jolley, Jennifer D. M.;Karpe, Fredrik;Keniry, Andrew;Khaw, Kay-Tee;Luben, Robert N.;Mangino, Massimo;Marchini, Jonathan;McArdle, Wendy L.;McGinnis, Ralph;Meyre, David;Munroe, Patricia B.;Morris, Andrew D.;Ness, Andrew R.;Neville, Matthew J.;Nica, Alexandra C.;Ong, Ken K.;O'Rahilly, Stephen;Owen, Katharine R.;Palmer, Colin N. A.;Papadakis, Konstantinos;Potter, Simon;Pouta, Anneli;Qi, Lu;Randall, Joshua C.;Rayner, Nigel W.;Ring, Susan M.;Sandhu, Manjinder S.;Scherag, Andre;Sims, Matthew A.;Song, Kijoung;Soranzo, Nicole;Speliotes, Elizabeth K.;Syddall, Holly E.;Teichmann, Sarah A.;Timpson, Nicholas J.;Tobias, Jonathan H.;Uda, Manuela;Vogel, Carla I. Ganz;Wallace, Chris;Waterworth, Dawn M.;Weedon, Michael N.;Willer, Cristen J.;Wraight, Vicki L.;Yuan, Xin;Zeggini, Eleftheria;Hirschhorn, Joel N.;Strachan, David P.;Ouwehand, Willem H.;Caulfield, Mark J.;Samani, Nilesh J.;Frayling, Timothy M.;Vollenweider, Peter;Waeber, Gerard;Mooser, Vincent;Deloukas, Panos;McCarthy, Mark I.;Wareham, Nicholas J.;Barroso, Ines
通讯作者：
Barroso, Ines