Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
文献类型：期刊论文
| 作者 | Turcot, Valerie130; Dube, Marie-Pierre130; Lo, Ken S.130; Rioux, John D.14,130; Tardif, Jean-Claude130; Lettre, Guillaume14,130; Lu, Yingchang131,132,133; Schurmann, Claudia132,133; Alfred, Tamuno132; Bottinger, Erwin P.132 |
| 刊名 | NATURE GENETICS
 |
| 出版日期 | 2018 |
| 卷号 | 50期号:1页码:26-41 |
| ISSN号 | 1061-4036 |
| DOI | 10.1038/s41588-017-0011-x |
| 文献子类 | Article |
| 英文摘要 | Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity. |
| 学科主题 | General & Internal Medicine |
| WOS关键词 | GENOME-WIDE ASSOCIATION ; MELANOCORTIN-4 RECEPTOR GENE ; SEVERE ALZHEIMERS-DISEASE ; DONEPEZIL 23 MG ; AMP ISOFORM 1 ; INSULIN SENSITIVITY ; FRAMESHIFT MUTATION ; GLUCOSE-HOMEOSTASIS ; HYPOTHALAMIC AMPK ; CODING VARIANTS |
| 语种 | 英语 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/715]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Broad Inst & MIT Harvard, Cambridge, MA 02142 USA; 2.Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands; 3.Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, Utrecht, Netherlands; 4.Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands; 5.Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands; 6.Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece; 7.Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA; 8.Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands; 9.Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands; 10.Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England; |
| 推荐引用方式 GB/T 7714 | Turcot, Valerie,Dube, Marie-Pierre,Lo, Ken S.,et al. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity[J]. NATURE GENETICS,2018,50(1):26-41. |
| APA | Turcot, Valerie.,Dube, Marie-Pierre.,Lo, Ken S..,Rioux, John D..,Tardif, Jean-Claude.,...&,.(2018).Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.NATURE GENETICS,50(1),26-41. |
| MLA | Turcot, Valerie,et al."Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity".NATURE GENETICS 50.1(2018):26-41. |
入库方式： OAI收割
来源：上海营养与健康研究所
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