在兩項研究中,，研究人員在東亞人體內(nèi)鑒定出一些常見性的與肥胖相關(guān)的遺傳變異型(genetic variant),。
在第一項研究中，通過分析來自62000多名東亞人的數(shù)據(jù),，研究人員在基因KLF9和MSTN中鑒定出這些變異型或者說單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)中的兩個,。KLF9是一種轉(zhuǎn)錄因子，能夠激活參與多種生理過程(包括一種參與脂肪細胞分化和與肥胖相關(guān)聯(lián)的過程)的基因表達,。已知MSTN突變導致身體脂肪減少,。進一步分析揭示這兩個新鑒定出的SNP相互作用，這就提示著MSTN調(diào)節(jié)KLF9對身體質(zhì)量指數(shù)(body mass index, BMI)產(chǎn)生的影響,。BMI是衡量肥胖的通行標準,。
在第二項研究中，研究人員對來自8項全基因組關(guān)聯(lián)研究的數(shù)據(jù)進行整合分析，涉及將近28000名東亞人基因組中大約240萬個SNP,。這項研究在三種已證實與BMI相關(guān)聯(lián)的基因FTO,、SEC16B和MC4R中鑒定出SNP。
在對來自另外55000名東亞人的數(shù)據(jù)進行分析之后,，來自日本理化學研究所的Yukinori Okada,、Toshihiro Tanaka和同事們著重關(guān)注他們發(fā)現(xiàn)與BMI相關(guān)聯(lián)的798個SNP，以及在較早前研究中發(fā)現(xiàn)與BMI相關(guān)聯(lián)的另外50個SNP,。通過將這些數(shù)據(jù)集結(jié)合在一起,，他們證實之前發(fā)現(xiàn)與歐洲人肥胖相關(guān)聯(lián)的6個基因中的SNP也顯著性地與東亞人BMI相關(guān)聯(lián)。
研究人員也鑒定出3個之前未知的與BMI顯著性相關(guān)聯(lián)的變異位于或靠近基因CDKAL1,、PCSK1和GP2,。
在這些所有被鑒定的變異型中，F(xiàn)TO變異型最為強烈地與BMI相關(guān)聯(lián),，而且它將近占參與研究者個體變異的0.2%,。這種變異型與9個與BMI相關(guān)聯(lián)的其他基因大約占研究參與者之間個體變異的0.9%，而全部22個被鑒定出的基因一起也只占研究參與者之間個體變異的1.18%,。
類似這樣的大規(guī)模研究提供關(guān)于肥胖遺傳基礎(chǔ)方面有價值的信息,。通過鑒定在東亞人體內(nèi)發(fā)揮重要作用的遺傳變異型，研究人員就可以將它們與歐洲人攜帶的遺傳型進行比較,。(生物谷：Bioon.com)
本文編譯自Finding genes that expand waistlines
doi: 10.1038/ng.1086
PMC:
PMID:
Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations
Yukinori Okada, Michiaki Kubo, Hiroko Ohmiya et al.
Obesity is a disorder with a complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index, the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here we report a genome-wide association study and replication studies with 62,245 east Asian subjects, which identified two new body mass index–associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 × 10−11) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 × 10−9), as well as several previously reported loci (the SEC16B, BDNF, FTO, MC4R and GIPR loci, P < 5.0 × 10−8). We subsequently performed gene-gene interaction analyses and identified an interaction (P = 2.0 × 10−8) between a SNP in the KLF9 locus (rs11142387) and one in the MSTN (also known as GDF8) locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.
doi: 10.1038/ng.1087
PMC:
PMID:
Meta-analysis identifies common variants associated with body mass index in east Asians
Wanqing Wen,Yoon-Shin Cho, Wei Zheng, Rajkumar Dorajoo et al.
Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.
