Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease

被引：76

作者：

Zheng, Jie ^{[1
]}

Zhang, Yuemiao ^{[2
]}

Rasheed, Humaira ^{[1
,3
]}

Walker, Venexia ^{[1
,4
]}

Sugawara, Yuka ^{[5
]}

Li, Jiachen ^{[6
]}

Leng, Yue ^{[7
]}

Elsworth, Benjamin ^{[1
]}

Wootton, Robyn E. ^{[1
]}

Fang, Si ^{[1
]}

Yang, Qian ^{[1
]}

Burgess, Stephen ^{[8
,9
]}

Haycock, Philip C. ^{[1
]}

Borges, Maria Carolina ^{[1
]}

Cho, Yoonsu ^{[1
]}

Carnegie, Rebecca ^{[1
]}

Howell, Amy ^{[1
]}

Robinson, Jamie ^{[1
]}

Thomas, Laurent F. ^{[3
,10
]}

Brumpton, Ben Michael ^{[1
,3
,11
]}

Hveem, Kristian ^{[3
]}

Hallan, Stein ^{[10
,12
]}

Franceschini, Nora ^{[13
]}

Morris, Andrew P. ^{[14
]}

Kottgen, Anna ^{[15
,16
]}

Pattaro, Cristian ^{[17
]}

Wuttke, Matthias ^{[15
,16
]}

Yamamoto, Masayuki ^{[18
,19
]}

Kashihara, Naoki ^{[20
]}

Akiyama, Masato ^{[21
,22
]}

Kanai, Masahiro ^{[23
,24
]}

Matsuda, Koichi ^{[25
]}

Kamatani, Yoichiro ^{[21
,26
]}

Okada, Yukinori ^{[24
,27
,28
]}

Walters, Robin ^{[29
,30
]}

Millwood, Iona Y. ^{[29
,30
]}

Chen, Zhengming ^{[29
,30
]}

Smith, George Davey ^{[1
,31
,32
]}

Barbour, Sean ^{[33
,34
]}

Yu, Canqing ^{[6
]}

Asvold, Bjorn Olav ^{[3
,35
]}

Zhang, Hong ^{[2
]}

Gaunt, Tom R. ^{[1
,31
,32
]}

机构：

[1] Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit IEU, Oakfield House, Bristol BS8 2BN, Avon, England

[2] Peking Univ First Hosp, Key Lab Renal Dis, Key Lab Chron Kidney Dis Prevent & Treatment,Mini, Renal Div,Peking Univ,Inst Nephrol,Minist Hlth Ch, Beijing, Peoples R China

[3] Norwegian Univ Sci & Technol, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway

[4] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA

[5] Univ Tokyo Hosp, Div Nephrol & Endocrinol, Tokyo, Japan

[6] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing, Peoples R China

[7] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA

[8] Cambridge Inst Publ Hlth, MRC Biostat Unit, Cambridge, England

[9] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England

[10] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, NTNU, Trondheim, Norway

[11] Trondheim Reg & Univ Hosp, Dept Thorac Med, St Olavs Hosp, Trondheim, Norway

[12] Trondheim Reg & Univ Hosp, Dept Nephrol, St Olavs Hosp, Trondheim, Norway

[13] Univ North Carolina, Dept Epidemiol, Chapel Hill, NC USA

[14] Univ Manchester, Div Musculoskeletal & Dermatol Sci, Manchester, Lancs, England

[15] Univ Freiburg, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Fac Med, Freiburg, Germany

[16] Univ Freiburg, Med Ctr, Freiburg, Germany

[17] Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy

[18] Tohoku Med Megabank Org, Sendai, Miyagi, Japan

[19] Tohoku Univ, Grad Sch Med, Sendai, Miyagi, Japan

[20] Kawasaki Med Sch, Dept Nephrol & Hypertens, Kurashiki, Okayama, Japan

[21] RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[22] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan

[23] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA

[24] Osaka Univ, Dept Stat Genet, Grad Sch Med, Suita, Osaka, Japan

[25] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Tokyo, Japan

[26] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Lab Complex Trait Genom, Tokyo, Japan

[27] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan

[28] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Suita, Osaka, Japan

[29] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England

[30] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England

[31] Univ Hosp Bristol NHS Fdn Trust, NIHR Biomed Res Ctr, Bristol, Avon, England

[32] Univ Bristol, Bristol, Avon, England

[33] Univ British Columbia, Div Nephrol, Vancouver, BC, Canada

[34] British Columbia Prov Renal Agcy, Vancouver, BC, Canada

[35] Trondheim Reg & Univ Hosp, Dept Endocrinol, Clin Med, St Olavs Hosp, Trondheim, Norway

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2021年 / 50卷 / 06期

基金：

国家自然科学基金重大研究计划; 英国医学研究理事会; 英国惠康基金; 国家重点研发计划; 英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 中国国家自然科学基金;

关键词：

chronic kidney disease; cardiometabolic risk factors; Mendelian randomization; causality; trans-ethnic study; BODY-MASS INDEX; DECREASED RENAL-FUNCTION; MACROVASCULAR DISEASE; LDL CHOLESTEROL; BLOOD-PRESSURE; SAMPLE-SIZE; RISK; PREVALENCE; LOCI; ASSOCIATION;

D O I：

10.1093/ije/dyab203

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Background: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. Methods: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included. Results: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m(2). Conclusions: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.

引用

页码：1995 / 2010

页数：16

共 88 条

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