Rare and low-frequency coding variants alter human adult height
文献类型：期刊论文
| 作者 | Marouli, Eirini274; Stirrups, Kathleen E.274; Caulfield, Mark J.274; Kanoni, Stavroula274; Munroe, Patricia B.205,274; Ntalla, Ioanna274; Warren, Helen R.205,274; Deloukas, Panos274; Graff, Mariaelisa273; Highland, Heather M.273 |
| 刊名 | NATURE
 |
| 出版日期 | 2017 |
| 卷号 | 542期号:7640页码:186-190 |
| 关键词 | Eplerenone TGF-beta(1) Atrial fibrosis Smad7 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature21039 |
| 文献子类 | Article |
| 英文摘要 | Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | GENOME-WIDE ASSOCIATION ; MISSING HERITABILITY ; GENETIC ARCHITECTURE ; INTERLEUKIN-11 ; MUTATIONS ; MICE |
| 语种 | 英语 |
| WOS记录号 | WOS:000393737500031 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/957]  |
| 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.Harvard Med Sch, Boston, MA 02115 USA; 2.Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark; 3.Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA; 4.Indiana Univ, Sch Med, Indianapolis, IN 46202 USA; 5.Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA; 6.Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA; 7.Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England; 8.MRL Merck Co Inc, Cardiometab Dis, Kenilworth, NJ 07033 USA; 9.Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA; 10.Univ Amsterdam, Dept Brain & Cognit, NL-1018 WS Amsterdam, Netherlands; |
| 推荐引用方式 GB/T 7714 | Marouli, Eirini,Stirrups, Kathleen E.,Caulfield, Mark J.,et al. Rare and low-frequency coding variants alter human adult height[J]. NATURE,2017,542(7640):186-190. |
| APA | Marouli, Eirini.,Stirrups, Kathleen E..,Caulfield, Mark J..,Kanoni, Stavroula.,Munroe, Patricia B..,...&,.(2017).Rare and low-frequency coding variants alter human adult height.NATURE,542(7640),186-190. |
| MLA | Marouli, Eirini,et al."Rare and low-frequency coding variants alter human adult height".NATURE 542.7640(2017):186-190. |
入库方式： OAI收割
来源：上海营养与健康研究所
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