A thrifty variant in CREBRF strongly influences body mass index in Samoans.
A thrifty variant in CREBRF strongly influences body mass index in Samoans.
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DOI：
10.1038/ng.3620
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发表时间：
2016-09
期刊：
影响因子：
30.8
通讯作者：
McGarvey, Stephen T.
中科院分区：
文献类型：
--
作者：
Minster, Ryan L.;Hawley, Nicola L.;Su, Chi -Ting;Sun, Guangyun;Kershaw, Erin E.;Cheng, Hong;Buhule, Olive D.;Lin, Jerome;Reupena, Muagututia Sefuiva;Viali, Satupditea;Tuitele, John;Naseri, Take;Urban, Zsolt;Deka, Ranjan;Weeks, Daniel E.;McGarvey, Stephen T.
萨摩亚人是一个独特的创始人群，肥胖的患病率很高，这使他们非常适合确定肥胖的新遗传因素。我们对3072名萨摩亚人进行了一项全基因组关联研究（GWAS），发现一种变异rs12513649与体重指数（BMI）密切相关（P = 5.3 × 10−14），并在另外2102名萨摩亚人中重复了这种关联（P = 1.2 × 10−9）。靶向测序在CREBRF中发现了一个强相关的错义变体rs373863828 (p.a g457gln) （meta P = 1.4 × 10−20）。尽管这种变异在其他人群中极为罕见，但在萨摩亚人中很常见（频率为0.259），其效应量远远大于任何其他已知的常见BMI风险变异（风险相关等位基因每个拷贝1.36-1.45 kg/m2）。与野生型CREBRF相比，在脂肪细胞模型中，Arg457Gln变异体在过表达时选择性地减少了能量使用并增加了脂肪储存。这些数据，结合编码p.a g457gln的等位基因正向选择的证据，支持了“节俭”变异假说是人类肥胖的一个因素。
Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10−14), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10−20). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36–1.45 kg/m2 per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity.
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影响因子：
9.8
作者：
Chen, Wei-Min;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
DOI：
10.1073/pnas.0501190102
发表时间：
2005-05-31
影响因子：
11.1
作者：
Dengjel, J;Schoor, O;Stevanovic, S
通讯作者：
Stevanovic, S
影响因子：
2.9
作者：
Keighley, ED;McGarvey, ST;Vial, S
通讯作者：
Vial, S
影响因子：
5.2
作者：
Heath, Simon C.;Gut, Ivo G.;Lathrop, Mark
通讯作者：
Lathrop, Mark
影响因子：
2
作者：
Gauderman, WJ
通讯作者：
Gauderman, WJ