Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure

被引：49

作者：

Siedlinski, Mateusz ^{[1
,2
,3
]}

Carnevale, Lorenzo ^{[4
]}

Xu, Xiaoguang ^{[5
]}

Carnevale, Daniela ^{[4
,6
]}

Evangelou, Evangelos ^{[7
,8
,9
]}

Caulfield, Mark J. ^{[10
]}

Maffia, Pasquale ^{[11
,12
]}

Wardlaw, Joanna ^{[13
]}

Samani, Nilesh J. ^{[14
,15
]}

Tomaszewski, Maciej ^{[5
,16
]}

Lembo, Giuseppe ^{[4
,6
]}

Holmes, Michael, V ^{[17
,18
]}

Guzik, Tomasz J. ^{[1
,2
,3
]}

机构：

[1] Jagiellonian Univ Med Coll, Dept Internal Med, Ul Skarbowa 1, PL-31121 Krakow, Poland

[2] Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland

[3] Jagiellonian Univ Med Coll, Ctr Med Genom OMICRON, Ul Kopernika 7c, PL-31034 Krakow, Poland

[4] IRCCS INM Neuromed, Dept Angiocardioneurol & Translat Med, Via Atinense 18, I-86077 Pozzilli, Italy

[5] Univ Manchester, Fac Biol Med & Hlth, Sch Med Sci, Div Cardiovasc Sci, 46 Grafton St, Manchester M13 9NT, England

[6] Sapienza Univ Rome, Dept Mol Med, Viale Regina Elena 291, I-00161 Rome, Italy

[7] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, South Kensington Campus, London SW7 2AZ, England

[8] Univ Ioannina, Univ Ioannina Med Sch, Dept Hyg & Epidemiol, Univ Campus,POB 1186, Ioannina 45110, Greece

[9] Fdn Res & Technol Hellas, Dept Biomed Res, Inst Mol Biol & Biotechnol, Univ Campus, GR-45115 Ioannina, Greece

[10] Queen Mary Univ London, William Harvey Res Inst, NIHR Biomed Res Ctr Barts, Charterhouse Sq, London EC1M 6BQ, England

[11] Univ Glasgow, Coll Med Vet & Life Sci, Sch Infect & Immun, Univ Ave, Glasgow G12 8QQ, Scotland

[12] Univ Naples Federico II, Sch Med & Surg, Dept Pharm, Via Domenico Montesano 49, I-80131 Naples, Italy

[13] Univ Edinburgh, UK Dementia Res Inst, Ctr Clin Brain Sci, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland

[14] Univ Leicester, Dept Cardiovasc Sci, Univ Rd, Leicester LE1 7RH, England

[15] Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Groby Rd, Leicester LE3 9QP, England

[16] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Oxford Rd, Manchester M13 9WL, England

[17] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Queens Rd, Bristol BS8 1QU, England

[18] Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Queens Rd, Bristol BS8 1QU, England

来源：

EUROPEAN HEART JOURNAL | 2023年 / 44卷 / 23期

基金：

英国医学研究理事会;

关键词：

Hypertension; Cognitive function; Blood pressure; Mendelian randomisation; Brain; Genome-wide association study; GENOME-WIDE ASSOCIATION; HYPERTENSION; PHENOTYPES; RISK; LOCI;

D O I：

10.1093/eurheartj/ehad101

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aims Observational studies have linked elevated blood pressure (BP) to impaired cognitive function. However, the functional and structural changes in the brain that mediate the relationship between BP elevation and cognitive impairment remain unknown. Using observational and genetic data from large consortia, this study aimed to identify brain structures potentially associated with BP values and cognitive function. Methods and results Data on BP were integrated with 3935 brain magnetic resonance imaging-derived phenotypes (IDPs) and cognitive function defined by fluid intelligence score. Observational analyses were performed in the UK Biobank and a prospective validation cohort. Mendelian randomisation (MR) analyses used genetic data derived from the UK Biobank, International Consortium for Blood Pressure, and COGENT consortium. Mendelian randomisation analysis identified a potentially adverse causal effect of higher systolic BP on cognitive function [-0.044 standard deviation (SD); 95% confidence interval (CI) -0.066, -0.021] with the MR estimate strengthening (-0.087 SD; 95% CI -0.132, -0.042), when further adjusted for diastolic BP. Mendelian randomisation analysis found 242, 168, and 68 IDPs showing significant (false discovery rate P < 0.05) association with systolic BP, diastolic BP, and pulse pressure, respectively. Most of these IDPs were inversely associated with cognitive function in observational analysis in the UK Biobank and showed concordant effects in the validation cohort. Mendelian randomisation analysis identified relationships between cognitive function and the nine of the systolic BP-associated IDPs, including the anterior thalamic radiation, anterior corona radiata, or external capsule. Conclusion Complementary MR and observational analyses identify brain structures associated with BP, which may be responsible for the adverse effects of hypertension on cognitive performance.

引用

页码：2114 / 2125

页数：12

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