A genome-wide association study of the frailty index highlights brain pathways in ageing.
A genome-wide association study of the frailty index highlights brain pathways in ageing.
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DOI：
10.1111/acel.13459
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发表时间：
2021-09
期刊：
影响因子：
7.8
通讯作者：
Pilling LC
中科院分区：
文献类型：
--
作者：
Atkins JL;Jylhävä J;Pedersen NL;Magnusson PK;Lu Y;Wang Y;Hägg S;Melzer D;Williams DM;Pilling LC
虚弱是一种常见的老年综合征，与残疾、死亡和住院密切相关。虚弱通常使用虚弱指数（FI）来衡量，该指数基于生命过程中许多健康缺陷的积累。FI的潜在机制是多因素的，并没有得到很好的理解，但遗传基础已被建议与遗传力估计在30%和45%之间。了解FI的遗传决定因素和生物学机制可能有助于延迟甚至预防虚弱。我们对欧洲血统英国生物库参与者（n = 164，610，60-70岁）和瑞典TwinGene参与者（n = 10，616，41-87岁）的虚弱指数进行了全基因组关联研究（GWAS）Meta分析。FI计算分别基于UK Biobank和TwinGene关于症状、残疾和诊断疾病的49或44个自我报告项目。14个位点与FI相关（p < 5*10 - 8）。许多FI相关基因座已经与体重指数、心血管疾病、吸烟、HLA蛋白、抑郁症和神经质等性状建立了关联;然而，其中一个似乎是新的。单核苷酸多态性（SNP）遗传度为11%（0.11，SE 0.005）。在富集分析中，在额叶皮层和海马中表达的基因显著下调（校正p < 0.05）。我们还使用孟德尔随机化来确定可能影响虚弱风险的可改变的特征和暴露，较高的教育程度遗传风险评分与较低的虚弱程度相关。脆弱的风险受到许多遗传因素的影响，包括众所周知的疾病风险因素和心理健康，特别强调大脑中的通路。这项全基因组关联研究对UK Biobank和TwinGene中的脆弱指数（FI）进行了Meta分析，确定了14个与FI相关的基因座。许多FI相关基因座与众所周知的疾病风险因素（如BMI、心血管疾病、吸烟、HLA蛋白、抑郁症和神经质）建立了关联。1是小说。脆弱的风险受到许多遗传因素的影响，包括众所周知的疾病风险因素和心理健康，特别强调大脑中的通路。
Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome‐wide association study (GWAS) meta‐analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self‐reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10−8). Many FI‐associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well‐known disease risk factors and mental health, with particular emphasis on pathways in the brain. This genome‐wide association study meta‐analysis of the frailty index (FI) in UK Biobank and TwinGene, identified 14 loci associated with the FI. Many FI‐associated loci have established associations with well‐known disease risk factors such as BMI, cardiovascular disease, smoking, HLA proteins, depression and neuroticism. However 1 was novel. Risk of frailty is influenced by many genetic factors, including well‐known disease risk factors and mental health, with particular emphasis on pathways in the brain.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
6.7
作者：
Livshits G;Ni Lochlainn M;Malkin I;Bowyer R;Verdi S;Steves CJ;Williams FMK
通讯作者：
Williams FMK
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
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.
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL