Nature Genetics：一种基因变异可增加肥胖风险

生物谷报道：英国维康信托基金会桑格研究所等机构的科学家通过一项9万人参与的实验确定一种与肥胖相关的基因，这个基因变异会导致肥胖的发生。

研究论文发表在最新一期的《自然·遗传学》上面，这种新确定的基因位于人类基因组中的“垃圾ＤＮＡ”（生物谷注：内含子）区域，非常接近另外一种肥胖基因ＭＣ４Ｒ，其变种会阻止ＭＣ４Ｒ基因正常表达。研究人员对９万人的基因进行研究后发现，拥有这种新基因两种变异版本的人更容易长胖。

研究人员说，这一发现说明，占据人类基因组绝大部分区域的“垃圾ＤＮＡ”极其重要。“垃圾ＤＮＡ”是指人体内的非编码ＤＮＡ，它们不像编码基因那样控制产生特定的蛋白质。

研究人员认为，“垃圾ＤＮＡ”包含可改变基因活动并影响蛋白质制造的遗传开关，而此次新发现的基因本身可能就是一种遗传开关。（生物谷：www.bioon.com）

生物谷推荐原始出处：

Nature Genetics (04 May 2008), doi: 10.1038/ng.140, Letters

Common variants near MC4R are associated with fat mass, weight and risk of obesity

Ruth J F Loos^1,^2,⁷³, Cecilia M Lindgren^3,^4,⁷³, Shengxu Li^1,^2,⁷³, Eleanor Wheeler⁵, Jing Hua Zhao^1,², Inga Prokopenko^3,⁴, Michael Inouye⁵, Rachel M Freathy^6,⁷, Antony P Attwood^5,⁸, Jacques S Beckmann^9,¹⁰, Sonja I Berndt¹¹, The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial⁷¹, Sven Bergmann^9,¹², Amanda J Bennett^3,⁴, Sheila A Bingham¹³, Murielle Bochud¹⁴, Morris Brown¹⁵, Stéphane Cauchi¹⁶, John M Connell¹⁷, Cyrus Cooper¹⁸, George Davey Smith¹⁹, Ian Day¹⁸, Christian Dina¹⁶, Subhajyoti De²⁰, Emmanouil T Dermitzakis⁵, Alex S F Doney²¹, Katherine S Elliott³, Paul Elliott^22,²³, David M Evans^3,¹⁹, I Sadaf Farooqi^2,²⁴, Philippe Froguel^16,²⁵, Jilur Ghori⁵, Christopher J Groves^3,⁴, Rhian Gwilliam⁵, David Hadley²⁶, Alistair S Hall²⁷, Andrew T Hattersley^6,⁷, Johannes Hebebrand²⁸, Iris M Heid^29,³⁰, KORA⁷¹, Blanca Herrera^3,⁴, Anke Hinney²⁸, Sarah E Hunt⁵, Marjo-Riitta Jarvelin^22,^23,³¹, Toby Johnson^9,^12,¹⁴, Jennifer D M Jolley⁸, Fredrik Karpe⁴, Andrew Keniry⁵, Kay-Tee Khaw³², Robert N Luben³², Massimo Mangino³³, Jonathan Marchini³⁴, Wendy L McArdle³⁵, Ralph McGinnis⁵, David Meyre¹⁶, Patricia B Munroe³⁶, Andrew D Morris²¹, Andrew R Ness³⁷, Matthew J Neville⁴, Alexandra C Nica⁵, Ken K Ong^1,², Stephen O'Rahilly^2,²⁴, Katharine R Owen⁴, Colin N A Palmer³⁸, Konstantinos Papadakis²⁶, Simon Potter⁵, Anneli Pouta^31,³⁹, Lu Qi⁴⁰, Nurses' Health Study⁷¹, Joshua C Randall^3,⁴, Nigel W Rayner^3,⁴, Susan M Ring³⁵, Manjinder S Sandhu^1,³², André Scherag⁴¹, Matthew A Sims^1,², Kijoung Song⁴², Nicole Soranzo⁵, Elizabeth K Speliotes^43,⁴⁴, Diabetes Genetics Initiative⁷¹, Holly E Syddall¹⁸, Sarah A Teichmann²⁰, Nicholas J Timpson^3,¹⁹, Jonathan H Tobias⁴⁵, Manuela Uda⁴⁶, The SardiNIA Study⁷¹, Carla I Ganz Vogel²⁸, Chris Wallace³⁶, Dawn M Waterworth⁴², Michael N Weedon^6,⁷, The Wellcome Trust Case Control Consortium⁷², Cristen J Willer⁴⁷, FUSION⁷¹, Vicki L Wraight^2,²⁴, Xin Yuan⁴², Eleftheria Zeggini³, Joel N Hirschhorn^44,^48,^49,^50,⁵¹, David P Strachan²⁶, Willem H Ouwehand⁸, Mark J Caulfield³⁶, Nilesh J Samani³³, Timothy M Frayling^6,⁷, Peter Vollenweider⁵², Gerard Waeber⁵², Vincent Mooser⁴², Panos Deloukas⁵, Mark I McCarthy^3,^4,⁷³, Nicholas J Wareham^1,^2,⁷³ & Inês Barroso^5,⁷³

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 times 10^{- 6}) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 times 10^{- 15}) and 5,988 children aged 7–11 (0.13 Z-score units; P = 1.5 times 10^{- 8}). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 times 10^{- 11}). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 times 10^{- 4}). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.