Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: A meta-analysis

JAMA - Journal of the American Medical Association

Volumn 316, Issue 13, 2016, Pages 1383-1391

  Lotta, Luca A ^a   Sharp, Stephen J ^a   Burgess, Stephen ^a   Perry, John R B ^a   Stewart, Isobel D ^a   Willems, Sara M ^a   Luan, Jian'an ^a   Ardanaz, Eva ^b,c,d   Arriola, Larraitz ^e,f,g   Balkau, Beverley ^h,i   Boeing, Heiner ^j   Deloukas, Panos ^k   Forouhi, Nita G ^a   Franks, Paul W ^l,m   Grioni, Sara ⁿ   Kaaks, Rudolf ^o   Key, Timothy J ^p   Navarro, Carmen ^e,q,r   Nilsson, Peter M ^l   Overvad, Kim ^s,t   Palli, Domenico ^u   Panico, Salvatore ^v   Quirós, Jose Ramón ^w   Riboli, Elio ^x   Rolandsson, Olov ^m   Sacerdote, Carlotta ^y,z   Salamanca Fernandez, Elena ^e,aa,ab   Slimani, Nadia ^ac   Spijkerman, Annemieke M W ^ad   Tjonneland, Anne ^ae   Tumino, Rosario ^af   Van Der A, Daphne L ^ad   Van Der Schouw, Yvonne T ^ag   McCarthy, Mark I ^ag   Barroso, Inês ^k   O'Rahilly, Stephen ^a   Savage, David B ^a   Sattar, Naveed ^ah   Langenberg, Claudia ^a   Scott, Robert A ^a   Wareham, Nicholas J ^a   more..

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b INSTITUTO DE SALUD PÚBLICA DE NAVARRA   (Spain)

^c Recinto de Complejo Hospitalario de Navarra   (Spain)

^d CIBER EPIDEMIOLOGÍA Y SALUD PÚBLICA CIBERESP   (Spain)

^e Public Health Division of Gipuzkoa   (Spain)

^f BIODONOSTIA HEALTH RESEARCH INSTITUTE   (Spain)

^g CENTRE FOR RESEARCH IN EPIDEMIOLOGY AND POPULATION HEALTH   (France)

^h UNIVERSITÉ PARIS SACLAY   (France)

ⁱ GERMAN INSTITUTE OF HUMAN NUTRITION   (Germany)

^j WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^k LUND UNIVERSITY   (Sweden)

^l UMEÅ UNIVERSITY   (Sweden)

^m Epidemiology Unit   (Italy)

ⁿ GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^o UNIVERSITY OF OXFORD   (United Kingdom)

^p DEPARTMENT OF EPIDEMIOLOGY   (Spain)

^q UNIVERSITY OF MURCIA   (Spain)

^r AARHUS UNIVERSITY   (Denmark)

^s AALBORG UNIVERSITY HOSPITAL   (Denmark)

^t CANCER RESEARCH AND PREVENTION INSTITUTE ISPO   (Italy)

^u UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^v PHD   (Spain)

^w IMPERIAL COLLEGE LONDON   (United Kingdom)

^x UNIVERSITY OF TURIN   (Italy)

^y Human Genetics Foundation   (Italy)

^z ANDALUSIAN SCHOOL OF PUBLIC HEALTH   (Spain)

^aa Instituto de Investigación Biosanitaria de Granada   (Spain)

^ab INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

^ac NATIONAL INSTITUTE FOR PUBLIC HEALTH AND THE ENVIRONMENT   (Netherlands)

^ad DANISH CANCER SOCIETY RESEARCH CENTER   (Denmark)

^ae Azienda sanitaria provinciale (ASP)   (Italy)

^af UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^ag UNIVERSITY OF OXFORD   (United Kingdom)

^ah UNIVERSITY OF GLASGOW   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER G5; ABC TRANSPORTER G8; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; ABCG5 PROTEIN, HUMAN; EZETIMIBE; HMGCR PROTEIN, HUMAN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LDLR PROTEIN, HUMAN; LIPOPROTEIN; MEMBRANE PROTEIN; NPC1L1 PROTEIN, HUMAN; PCSK9 PROTEIN, HUMAN; PROPROTEIN CONVERTASE 9; SIMVASTATIN;

ABCG5 GENE; ABCG8 GENE; ADULT; AGED; ALLELE; ARTICLE; CONTROLLED STUDY; CORONARY ARTERY DISEASE; EUROPE; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HMGCR GENE; HUMAN; LDLR GENE; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NPC1L1 GENE; PATHOGENESIS; PCSK9 GENE; PRIORITY JOURNAL; UNITED STATES; ADVERSE EFFECTS; BLOOD; COHORT ANALYSIS; COMBINATION DRUG THERAPY; GENETIC ASSOCIATION STUDY; GENETIC POLYMORPHISM; GENETIC VARIATION; GENETICS; META ANALYSIS; MIDDLE AGED; ODDS RATIO; RISK;

ADULT; AGED; ATP BINDING CASSETTE TRANSPORTER, SUB-FAMILY G, MEMBER 5; CHOLESTEROL, LDL; COHORT STUDIES; CORONARY ARTERY DISEASE; DIABETES MELLITUS, TYPE 2; DRUG THERAPY, COMBINATION; EZETIMIBE; GENETIC ASSOCIATION STUDIES; GENETIC VARIATION; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIPOPROTEINS; MEMBRANE PROTEINS; MIDDLE AGED; ODDS RATIO; POLYMORPHISM, GENETIC; PROPROTEIN CONVERTASE 9; RECEPTORS, LDL; RISK; SIMVASTATIN;

EID: 84995776151     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.2016.14568     Document Type: Article

References (42)

1. Stone NJ, Robinson JG, Lichtenstein AH, et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults. Ann Intern Med. 2014;160(5):339-343.
2. Fulcher J, O'Connell R, VoyseyM, et al. Efficacy and safety of LDL-lowering therapy among men and women. Lancet. 2015;385(9976):1397-1405.
3. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes. Lancet. 2010;375(9716): 735-742.
4. Preiss D, Seshasai SR,Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. JAMA. 2011;305 (24):2556-2564.
5. Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight. Lancet. 2015;385 (9965):351-361.
6. Jarcho JA, Keaney JF Jr. Proof that lower is better. N Engl J Med. 2015;372(25):2448-2450.
7. Cannon CP, BlazingMA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25): 2387-2397.
8. Nelson MR, Tipney H, Painter JL, et al. The support of human genetic evidence for approved drug indications. Nat Genet. 2015;47(8):856-860.
9. Plenge RM, Scolnick EM, Altshuler D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov. 2013;12(8):581-594.
10. Scott RA, Freitag DF, Li L, et al. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Sci Transl Med. 2016;8(341): 341ra76.
11. Ference BA, Majeed F, Penumetcha R, et al. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both. J Am Coll Cardiol. 2015;65(15):1552-1561.
12. Stitziel NO,Won HH, Morrison AC, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371 (22):2072-2082.
13. Langenberg C, Sharp S, Forouhi NG, et al. Design and cohort description of the InterAct Project. Diabetologia. 2011;54(9):2272-2282.
14. Collins R. What makes UK Biobank special? Lancet. 2012;379(9822):1173-1174.
15. Morris AP, Voight BF, Teslovich TM, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981-990.
16. Smith GD, Ebrahim S. 'Mendelian randomization.' Int J Epidemiol. 2003;32(1):1-22.
17. Burgess S, Dudbridge F, Thompson SG. Combining information on multiple instrumental variables in Mendelian randomization. Stat Med. 2016;35(11):1880-1906.
18. Willer CJ, Schmidt EM, Sengupta S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45(11):1274-1283.
19. NikpayM, Goel A,Won HH, et al. A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47(10): 1121-1130.
20. Scott RA, Lagou V,Welch RP, et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012;44 (9):991-1005.
21. Manning AK, HivertMF, Scott RA, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012;44(6):659-669.
22. Saxena R, HivertMF, Langenberg C, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42(2):142-148.
23. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-206.
24. Shungin D, Winkler TW, Croteau-Chonka DC, et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015;518 (7538):187-196.
25. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88(1):76-82.
26. Yang J, Ferreira T, Morris AP, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet. 2012;44(4):369-375, S1-S3.
27. Gray KA, Yates B, Seal RL,WrightMW, Bruford EA. Genenames.org: the HGNC resources in 2015. Nucleic Acids Res. 2015;43(Database issue): D1079-D1085.
28. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O'Donnell CJ, de Bakker PI. SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics. 2008;24(24):2938-2939.
29. Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26(17):2190-2191.
30. Takeshita Y, Takamura T, Honda M, et al. The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia. 2014;57(5):878-890.
31. Blazing MA; IMPROVE-IT Investigators. Incidence of new onset diabetes in the IMPROVE-IT trial: does adding ezetimibe to simvastatin increase risk compared to simvastatin alone? European Society of Cardiology Congress 2015. http://congress365.escardio.org/Search-Results ?vgnextkeyword=C365PRESENTATION124439# .V0iX-FUrKUl
32. Fall T, XieW, PoonW, et al. Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes. Diabetes. 2015;64(7):2676-2684.
33. Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA. 2015;313(10):1029-1036.
34. Davis HR Jr, Zhu LJ, Hoos LM, et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem. 2004;279(32):33586-33592.
35. Brown MS, Goldstein JL. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res. 1980;21(5):505-517.
36. Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A. 2004;101(18):7100-7105.
37. Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem. 2004;279(47):48865-48875.
38. Brunham LR, Kruit JK, Pape TD, et al. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat Med. 2007;13(3):340-347.
39. Labonté ED, Camarota LM, Rojas JC, et al. Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc1l1-/-mice. Am J Physiol Gastrointest Liver Physiol. 2008;295(4):G776-G783.
40. Kurano M, HaraM, Satoh H, Tsukamoto K. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis. Metabolism. 2015;64(5):588-596.
41. Bonnefond A, Yengo L, LeMay C, et al. The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis. Diabetologia. 2015;58(9):2051-2055.
42. Kathiresan S. Developing medicines that mimic the natural successes of the human genome: lessons from NPC1L1, HMGCR, PCSK9, APOC3, and CETP. J AmColl Cardiol. 2015;65(15):1562-1566.