Genetic basis of falling risk susceptibility in the UK Biobank Study.
Genetic basis of falling risk susceptibility in the UK Biobank Study.
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英国生物库研究中风险易感性下降的遗传基础。
DOI：
10.1038/s42003-020-01256-x
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发表时间：
2020-09-30
影响因子：
5.9
通讯作者：
Rivadeneira F
中科院分区：
文献类型：
--
作者：
Trajanoska K;Seppala LJ;Medina-Gomez C;Hsu YH;Zhou S;van Schoor NM;de Groot LCPGM;Karasik D;Richards JB;Kiel DP;Uitterlinden AG;Perry JRB;van der Velde N;Day FR;Rivadeneira F
外在因素和内在因素都容易使老年人跌倒。我们进行了一项全基因组关联分析，以调查来自英国生物库研究的89,076例患者和362,103名对照中，个人跌倒易感性的多少可归因于遗传学。分析揭示了一个小但显著的基于SNP的遗传度(2.7%)，并确定了三个新的与跌倒相关的基因座(P组合 ≤ 5 × 10−8)。两个独立环境中的多基因风险得分显示出多基因遗传模式。跌倒的风险与骨折有正的遗传相关性，首次发现了一条独立于骨密度的途径。失眠、神经质、抑郁症状和不同的药物也有正的遗传相关性。与肌肉力量、智力和主观幸福感呈负遗传相关。大脑，特别是小脑组织，显示出与跌倒相关的变体的最高基因表达丰富。总体而言，尽管跌倒风险具有高度异质性，但有一部分易感性可归因于遗传。Katerina Trajanoska等人。报告了一项关于英国生物库参与者自我报告的跌倒的全基因组关联研究。他们发现了三个新的与跌倒相关的基因座，发现跌倒的风险显示出多基因遗传模式，基于SNP的遗传率为2.7%。
Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual’s fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a small, but significant SNP-based heritability (2.7%) and identified three novel fall-associated loci (Pcombined ≤ 5 × 10−8). Polygenic risk scores in two independent settings showed patterns of polygenic inheritance. Risk of falling had positive genetic correlations with fractures, identifying for the first time a pathway independent of bone mineral density. There were also positive genetic correlations with insomnia, neuroticism, depressive symptoms, and different medications. Negative genetic correlations were identified with muscle strength, intelligence and subjective well-being. Brain, and in particular cerebellum tissue, showed the highest gene expression enrichment for fall-associated variants. Overall, despite the highly heterogenic nature underlying fall risk, a proportion of the susceptibility can be attributed to genetics. Katerina Trajanoska et al. report a genome-wide association study of self-reported falls in UK Biobank participants. They identify three novel fall-associated loci and find that risk of falling shows patterns of polygenic inheritance and a SNP-based heritability of 2.7%.
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影响因子：
64.8
作者：
Horikoshi, Momoko;Beaumont, Robin N.;Day, Felix R.;Warrington, Nicole M.;Kooijman, Marjolein N.;Fernandez-Tajes, Juan;Feenstra, Bjarke;van Zuydam, Natalie R.;Gaulton, Kyle J.;Grarup, Niels;Bradfield, Jonathan P.;Strachan, David P.;Li-Gao, Ruifang;Ahluwalia, Tarunveer S.;Kreiner, Eskil;Rueedi, Rico;Lyytikainen, Leo-Pekka;Cousminer, Diana L.;Wu, Ying;Thiering, Elisabeth;Wang, Carol A.;Have, Christian T.;Hottenga, Jouke-Jan;Vilor-Tejedor, Natalia;Joshi, Peter K.;Boh, Eileen Tai Hui;Ntalla, Ioanna;Pitkanen, Niina;Mahajan, Anubha;van Leeuwen, Elisabeth M.;Joro, Raimo;Lagou, Vasiliki;Nodzenski, Michael;Diver, Louise A.;Zondervan, Krina T.;Bustamante, Mariona;Marques-Vidal, Pedro;Mercader, Josep M.;Bennett, Amanda J.;Rahmioglu, Nilufer;Nyholt, Dale R.;Ma, Ronald C. W.;Tam, Claudia H. T.;Tam, Wing Hung;Ganesh, Santhi K.;van Rooij, Frank J. A.;Jones, Samuel E.;Loh, Po-Ru;Ruth, Katherine S.;Tuke, Marcus A.;Tyrrell, Jessica;Wood, Andrew R.;Yaghootkar, Hanieh;Scholtens, Denise M.;Paternoster, Lavinia;Prokopenko, Inga;Kovacs, Peter;Atalay, Mustafa;Willems, Sara M.;Panoutsopoulou, Kalliope;Wang, Xu;Carstensen, Lisbeth;Geller, Frank;Schraut, Katharina E.;Murcia, Mario;van Beijsterveldt, Catharina E. M.;Willemsen, Gonneke;Appel, Emil V. R.;Fonvig, Cilius E.;Trier, Caecilie;Tiesler, Carla M. T.;Standl, Marie;Kutalik, Zoltan;Bonas-Guarch, Silvia;Hougaard, David M.;Sanchez, Friman;Torrents, David;Waage, Johannes;Hollegaard, Mads V.;de Haan, Hugoline G.;Rosendaal, Frits R.;Medina-Gomez, Carolina;Ring, Susan M.;Hemani, Gibran;McMahon, George;Robertson, Neil R.;Groves, Christopher J.;Langenberg, Claudia;Luan, Jian'an;Scott, Robert A.;Zhao, Jing Hua;Mentch, Frank D.;MacKenzie, Scott M.;Reynolds, Rebecca M.;Lowe, William L.;Toenjes, Anke;Stumvoll, Michael;Lindi, Virpi;Lakka, Timo A.;van Duijn, Cornelia M.;Kiess, Wieland;Koerner, Antje;Sorensen, Thorkild I. A.;Niinikoski, Harri;Pahkala, Katja;Raitakari, Olli T.;Zeggini, Eleftheria;Dedoussis, George V.;Teo, Yik-Ying;Saw, Seang-Mei;Melbye, Mads;Campbell, Harry;Wilson, James F.;Vrijheid, Martine;de Geus, Eco J. C. N.;Boomsma, Dorret I.;Kadarmideen, Haja N.;Holm, Jens-Christian;Hansen, Torben;Sebert, Sylvain;Hattersley, Andrew T.;Beilin, Lawrence J.;Newnham, John P.;Pennell, Craig E.;Heinrich, Joachim;Adair, Linda S.;Borja, Judith B.;Mohlke, Karen L.;Eriksson, Johan G.;Widen, Elisabeth;Kahonen, Mika;Viikari, Jorma S.;Lehtimaki, Terho;Vollenweider, Peter;Bonnelykke, Klaus;Bisgaard, Hans;Mook-Kanamori, Dennis O.;Hofman, Albert;Rivadeneira, Fernando;Uitterlinden, Andre G.;Pisinger, Charlotta;Pedersen, Oluf;Power, Christine;Hyppoenen, Elina;Wareham, Nicholas J.;Hakonarson, Hakon;Davies, Eleanor;Walker, Brian R.;Jaddoe, Vincent W. V.;Jaervelin, Marjo-Riitta;Grant, Struan F. A.;Vaag, Allan A.;Lawlor, Debbie A.;Frayling, Timothy M.;Smith, George Davey;Morris, Andrew P.;Ong, Ken K.;Felix, Janine F.;Timpson, Nicholas J.;Perry, John R. B.;Evans, David M.;McCarthy, Mark I.;Freathy, Rachel M.
通讯作者：
Freathy, Rachel M.
影响因子：
30.8
作者：
Caubit, Xavier;Gubellini, Paolo;Andrieux, Joris;Roubertoux, Pierre L.;Metwaly, Mehdi;Jacq, Bernard;Fatmi, Ahmed;Had-Aissouni, Laurence;Kwan, Kenneth Y.;Salin, Pascal;Carlier, Michele;Lieden, Agne;Rudd, Eva;Shinawi, Marwan;Vincent-Delorme, Catherine;Cuisset, Jean-Marie;Lemaitre, Marie-Pierre;Abderrehamane, Fatimetou;Duban, Benedicte;Lemaitre, Jean-Francois;Woolf, Adrian S.;Bockenhauer, Detlef;Severac, Dany;Dubois, Emeric;Zhu, Ying;Sestan, Nenad;Garratt, Alistair N.;Goff, Lydia Kerkerian-Le;Fasano, Laurent
通讯作者：
Fasano, Laurent
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL