Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease

European Heart Journal

Volumn 39, Issue 23, 2018, Pages 2172-2178

  Helgadottir, Anna ^a   Sulem, Patrick ^a   Thorgeirsson, Gudmundur ^a,b,c   Gretarsdottir, Solveig ^a   Thorleifsson, Gudmar ^a   Jensson, Brynjar Ö ^a   Arnadottir, Gudny A ^a   Olafsson, Isleifur ^c   Eyjolfsson, Gudmundur I ^d   Sigurdardottir, Olof ^e   Thorsteinsdottir, Unnur ^a,b   Gudbjartsson, Daniel F ^a,b   Holm, Hilma ^a   Stefansson, Kari ^a,b  

^a DECODE GENETICS   (Iceland)

^b UNIVERSITY OF ICELAND   (Iceland)

^c LANDSPITALI UNIVERSITY HOSPITAL   (Iceland)

^d RAM   (Iceland)

^e AKUREYRI HOSPITAL   (Iceland)

Author keywords

Coronary artery disease; HDL cholesterol; Mutation; SR BI

Indexed keywords

HIGH DENSITY LIPOPROTEIN CHOLESTEROL; SCAVENGER RECEPTOR BI; SCARB1 PROTEIN, HUMAN; SCAVENGER RECEPTOR B;

ALLELE; ARTICLE; CARDIOVASCULAR RISK; CODING; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DISEASE ASSOCIATION; GENE FREQUENCY; GENE FUNCTION; GENE LOCUS; GENE MUTATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; ICELAND; MAJOR CLINICAL STUDY; PRIORITY JOURNAL; SCARB1 GENE; GENETICS; LIVER; METABOLISM; MUTATION;

CHOLESTEROL, HDL; CORONARY ARTERY DISEASE; HUMANS; ICELAND; LIVER; MUTATION; SCAVENGER RECEPTORS, CLASS B;

EID: 85048758413     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehy169     Document Type: Article

References (46)

1. Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J 2016; 37:3232-3245.
2. Emerging Risk Factors Collaboration, Angelantonio ED, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.
3. Brunham LR, Hayden MR. Human genetics of HDL: insight into particle metabolism and function. Prog Lipid Res 2015;58:14-25.
4. Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hó lm H, Ding EL, Johnson T, Schunkert H, Samani NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, Newton-Cheh C, Musunuru K, Pirruccello JP, Saleheen D, Chen L, Stewart AFR, Schillert A, Thorsteinsdottir U, Thorgeirsson G, Anand S, Engert JC, Morgan T, Spertus J, Stoll M, Berger K, Martinelli N, Girelli D, McKeown PP, Patterson CC, Epstein SE, Devaney J, Burnett M-S, Mooser V, Ripatti S, Surakka I, Nieminen MS, Sinisalo J, Lokki M-L, Perola M, Havulinna A, de Faire U, Gigante B, Ingelsson E, Zeller T, Wild P, de Bakker PIW, Klungel OH, Maitland-van der Zee A-H, Peters BJM, de Boer A, Grobbee DE, Kamphuisen PW, Deneer VHM, Elbers CC, Onland-Moret NC, Hofker MH, Wijmenga C, Verschuren WMM, Boer JMA, van der Schouw YT, Rasheed A, Frossard P, Demissie S, Willer C, Do R, Ordovas JM, Abecasis GR, Boehnke M, Mohlke KL, Daly MJ, Guiducci C, Burtt NP, Surti A, Gonzalez E, Purcell S, Gabriel S, Marrugat J, Peden J, Erdmann J, Diemert P, Willenborg C, Kö nig IR, Fischer M, Hengstenberg C, Ziegler A, Buysschaert I, Lambrechts D, Van de Werf F, Fox KA, El Mokhtari NE, Rubin D, Schrezenmeir J, Schreiber S, Schäfer A, Danesh J, Blankenberg S, Roberts R, McPherson R, Watkins H, Hall AS, Overvad K, Rimm E, Boerwinkle E, Tybjaerg-Hansen A, Cupples LA, Reilly MP, Melander O, Mannucci PM, Ardissino D, Siscovick D, Elosua R, Stefansson K, O'Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz SM, Altshuler D, Kathiresan S. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet 2012;380:572-580.
5. Helgadottir A, Gretarsdottir S, Thorleifsson G, Hjartarson E, Sigurdsson A, Magnusdottir A, Jonasdottir A, Kristjansson H, Sulem P, Oddsson A, Sveinbjornsson G, Steinthorsdottir V, Rafnar T, Masson G, Jonsdottir I, Olafsson I, Eyjolfsson GI, Sigurdardottir O, Daneshpour MS, Khalili D, Azizi F, Swinkels DW, Kiemeney L, Quyyumi AA, Levey AI, Patel RS, Hayek SS, Gudmundsdottir IJ, Thorgeirsson G, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease. Nat Genet 2016;48:634-639.
6. Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang H-Y, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkilä K, Hyppönen E, Isaacs A, Jackson AU, Johansson A , Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikäinen L-P, Magnusson PKE, Mangino M, Mihailov E, Montasser ME, Müller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen A-K, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney ASF, Dö ring A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen A-L, Hayward C, Hernandez D, Hicks AA, Holm H, Hung Y-J, Illig T, Jones MR, Kaleebu P, Kastelein JJP, Khaw K-T, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimäki T, Lin S-Y, Lindström J, Loos RJF, Mach F, McArdle WL, Meisinger C, Mitchell BD, Müller G, Nagaraja R, Narisu N, Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stancáková A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen Y-DI, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrieres J, Ferrucci L, Freimer NB, Gieger C, Groop LC, Gudnason V, Gyllensten U, Hamsten A, Harris TB, Hingorani A, Hirschhorn JN, Hofman A, Hovingh GK, Hsiung CA, Humphries SE, Hunt SC, Hveem K, Iribarren C, Järvelin M-R, Jula A, Kähönen M, Kaprio J, Kesäniemi A, Kivimaki M, Kooner JS, Koudstaal PJ, Krauss RM, Kuh D, Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Lind L, Lindgren CM, Martin NG, März W, McCarthy MI, McKenzie CA, Meneton P, Metspalu A, Moilanen L, Morris AD, Munroe PB, Njølstad I, Pedersen NL, Power C, Pramstaller PP, Price JF, Psaty BM, Quertermous T, Rauramaa R, Saleheen D, Salomaa V, Sanghera DK, Saramies J, Schwarz PEH, Sheu WH-H, Shuldiner AR, Siegbahn A, Spector TD, Stefansson K, Strachan DP, Tayo BO, Tremoli E, Tuomilehto J, Uusitupa M, van Duijn CM, Vollenweider P, Wallentin L, Wareham NJ, Whitfield JB, Wolffenbuttel BHR, Altshuler D, Ordovas JM, Boerwinkle E, Palmer CNA, Thorsteinsdottir U, Chasman DI, Rotter JI, Franks PW, Ripatti S, Cupples LA, Sandhu MS, Rich SS, Boehnke M, Deloukas P, Mohlke KL, Ingelsson E, Abecasis GR, Daly MJ, Neale BM, Kathiresan S. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013; 45:1345-1352.
7. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJP, Komajda M, Lopez-Sendon J, Mosca L, Tardif J-C, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-2122.
8. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJV, Mundl H, Nicholls SJ, Shah PK, Tardif J-C, Wright RS. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012;367:2089-2099.
9. Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-212.
10. Catapano AL, Graham I, Backer G, De Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Z, Riccardi G, Taskinen M-R, Tokgozoglu L, Verschuren WMM, Vlachopoulos C, Wood DA, Zamorano JL; ESC Scientific Document Group. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016;37:2999-3058.
11. Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder A. A S, Alam DS, Di Angelantonio E, Abecasis G, Chowdhury R, Erdmann J, Nordestgaard BG, Nielsen SF, Tybjærg-Hansen A, Schmidt RF, Kuulasmaa K, Liu DJ, Perola M, Blankenberg S, Salomaa V, Männistö S, Amouyel P, Arveiler D, Ferrieres J, Müller-Nurasyid M, Ferrario M, Kee F, Willer CJ, Samani N, Schunkert H, Butterworth AS, Howson JMM, Peloso GM, Stitziel NO, Danesh J, Kathiresan S, Rader DJ. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science 2016;351:1166-1171.
12. Couzin-Frankel J. LIPID BIOLOGY. Why high "good cholesterol" can be bad news. Science 2016;351:1126.
13. Trigatti BL, Hegele RA. Rare genetic variants and high-density lipoprotein: marching to a different drum. Arterioscler Thromb Vasc Biol 2016;36:e53-e55.
14. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271:518-520.
15. Kozarsky KF, Donahee MH, Rigotti A, Iqbal SN, Edelman ER, Krieger M. Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 1997;387:414-417.
16. Brundert M, Ewert A, Heeren J, Behrendt B, Ramakrishnan R, Greten H, Merkel M, Rinninger F. Scavenger receptor class B type I mediates the selective uptake of high-density lipoprotein-associated cholesteryl ester by the liver in mice. Arterioscler Thromb Vasc Biol 2005;25:143-148.
17. Ji Y, Wang N, Ramakrishnan R, Sehayek E, Huszar D, Breslow JL, Tall AR. Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile. J Biol Chem 1999;274: 33398-33402.
18. Trigatti B, Rayburn H, Vinals M, Braun A, Miettinen H, Penman M, Hertz M, Schrenzel M, Amigo L, Rigotti A, Krieger M. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci USA 1999;96:9322-9327.
19. Braun A, Trigatti BL, Post MJ, Sato K, Simons M, Edelberg JM, Rosenberg RD, Schrenzel M, Krieger M. Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein Edeficient mice. Circ Res 2002;90:270-276.
20. Ueda Y, Royer L, Gong E, Zhang J, Cooper PN, Francone O, Rubin EM. Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice. J Biol Chem 1999;274:7165-7171.
21. Arai T, Wang N, Bezouevski M, Welch C, Tall AR. Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. J Biol Chem 1999;274:2366-2371.
22. Kozarsky KF, Donahee MH, Glick JM, Krieger M, Rader DJ. Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 2000;20:721-727.
23. Fuchs M, Ivandic B, Müller O, Schalla C, Scheibner J, Bartsch P, Stange EF. Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI. Hepatology 2001; 33:1451-1459.
24. Vergeer M, Korporaal SJA, Franssen R, Meurs I, Out R, Hovingh GK, Hoekstra M, Sierts JA, Dallinga-Thie GM, Motazacker MM, Holleboom AG, Berkel TJCV, Kastelein JJP, Eck MV, Kuivenhoven JA. Genetic variant of the scavenger receptor BI in humans. N Engl J Med 2011;364:136-145.
25. Brunham LR, Tietjen I, Bochem AE, Singaraja RR, Franchini PL, Radomski C, Mattice M, Legendre A, Hovingh GK, Kastelein JJP, Hayden MR. Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans. Clin Genet 2011;79:575-581.
26. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee J-Y, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RYL, Wright AF, Witteman JCM, Wilson JF, Willemsen G, Wichmann H-E, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJG, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BWJH, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PKE, Lucas G, Luben R, Loos RJF, Lokki M-L, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, Kö nig IR, Khaw K-T, Kaprio J, Kaplan LM, Johansson A , Jarvelin MR, Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga J-J, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Dö ring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJC, de Faire U, Crawford G, Collins FS, Chen Y-D. I, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai E-S, Feranil AB, Kuzawa CW, Adair LS, Taylor HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJP, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010;466:707-713.
27. Marschall H-U, Einarsson C. Gallstone disease. J Intern Med 2007;261:529-542.
28. Styrkarsdottir U, Thorleifsson G, Sulem P, Gudbjartsson DF, Sigurdsson A, Jonasdottir A, Jonasdottir A, Oddsson A, Helgason A, Magnusson OT, Walters GB, Frigge ML, Helgadottir HT, Johannsdottir H, Bergsteinsdottir K, Ogmundsdottir MH, Center JR, Nguyen TV, Eisman JA, Christiansen C, Steingrimsson E, Jonasson JG, Tryggvadottir L, Eyjolfsson GI, Theodors A, Jonsson T, Ingvarsson T, Olafsson I, Rafnar T, Kong A, Sigurdsson G, Masson G, Thorsteinsdottir U, Stefansson K. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. Nature 2013;497:517-520.
29. Kong A, Masson G, Frigge ML, Gylfason A, Zusmanovich P, Thorleifsson G, Olason PI, Ingason A, Steinberg S, Rafnar T, Sulem P, Mouy M, Jonsson F, Thorsteinsdottir U, Gudbjartsson DF, Stefansson H, Stefansson K. Detection of sharing by descent, long-range phasing and haplotype imputation. Nat Genet 2008;40:1068-1075.
30. Kong A, Steinthorsdottir V, Masson G, Thorleifsson G, Sulem P, Besenbacher S, Jonasdottir A, Sigurdsson A, Kristinsson KT, Jonasdottir A, Frigge ML, Gylfason A, Olason PI, Gudjonsson SA, Sverrisson S, Stacey SN, Sigurgeirsson B, Benediktsdottir KR, Sigurdsson H, Jonsson T, Benediktsson R, Olafsson JH, Johannsson OT, Hreidarsson AB, Sigurdsson G, Ferguson-Smith AC, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Parental origin of sequence variants associated with complex diseases. Nature 2009;462:868-874.
31. Gudbjartsson DF, Helgason H, Gudjonsson SA, Zink F, Oddson A, Gylfason A, Besenbacher S, Magnusson G, Halldorsson BV, Hjartarson E, Sigurdsson GT, Stacey SN, Frigge ML, Holm H, Saemundsdottir J, Helgadottir HT, Johannsdottir H, Sigfusson G, Thorgeirsson G, Sverrisson JT, Gretarsdottir S, Walters GB, Rafnar T, Thjodleifsson B, Bjornsson ES, Olafsson S, Thorarinsdottir H, Steingrimsdottir T, Gudmundsdottir TS, Theodors A, Jonasson JG, Sigurdsson A, Bjornsdottir G, Jonsson JJ, Thorarensen O, Ludvigsson P, Gudbjartsson H, Eyjolfsson GI, Sigurdardottir O, Olafsson I, Arnar DO, Magnusson OT, Kong A, Masson G, Thorsteinsdottir U, Helgason A, Sulem P, Stefansson K. Large-scale whole-genome sequencing of the Icelandic population. Nat Genet 2015;47: 435-444.
32. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won H-H, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG; Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016;536:285-291.
33. von Kampen O, Buch S, Nothnagel M, Azocar L, Molina H, Brosch M, Erhart W, von Schö nfels W, Egberts J, Seeger M, Arlt A, Balschun T, Franke A, Lerch MM, Mayerle J, Kratzer W, Boehm BO, Huse K, Schniewind B, Tiemann K, Jiang Z-Y, Han T-Q, Mittal B, Srivastava A, Fenger M, Jørgensen T, Schirin-Sokhan R, Tö njes A, Wittenburg H, Stumvoll M, Kalthoff H, Lammert F, Tepel J, Puschel K, Becker T, Schreiber S, Platzer M, Vö lzke H, Krawczak M, Miquel JF, Schafmayer C, Hampe J. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus. Hepatology 2013; 57:2407-2417.
34. Webb TR, Erdmann J, Stirrups KE, Stitziel NO, Masca NGD, Jansen H, Kanoni S, Nelson CP, Ferrario PG, Kö nig IR, Eicher JD, Johnson AD, Hamby SE, Betsholtz C, Ruusalepp A, Franzén O, Schadt EE, Björkegren JLM, Weeke PE, Auer PL, Schick UM, Lu Y, Zhang H, Dube M-P, Goel A, Farrall M, Peloso GM, Won H-H, Do R, van Iperen E, Kruppa J, Mahajan A, Scott RA, Willenborg C, Braund PS, van Capelleveen JC, Doney ASF, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano N, Denny JC, Shaffer C, El-Mokhtari NE, Franke A, Heilmann S, Hengstenberg C, Hoffmann P, Holmen OL, Hveem K, Jansson J-H, Jö ckel K-H, Kessler T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, McCarthy MI, Van Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher SA, Alver M, Moebus S, Morris AD, Virtamo J, Nikpay M, Olivieri O, Provost S, AlQarawi A, Robertson NR, Akinsansya KO, Reilly DF, Vogt TF, Yin W, Asselbergs FW, Kooperberg C, Jackson RD, Stahl E, Müller-Nurasyid M, Strauch K, Varga TV, Waldenberger M, Zeng L, Chowdhury R, Salomaa V, Ford I, Jukema JW, Amouyel P, Kontto J, Nordestgaard BG, Ferrieres J, Saleheen D, Sattar N, Surendran P, Wagner A, Young R, Howson JMM, Butterworth AS, Danesh J, Ardissino D, Bottinger EP, Erbel R, Franks PW, Girelli D, Hall AS, Hovingh GK, Kastrati A, Lieb W, Meitinger T, Kraus WE, Shah SH, McPherson R, Orho-Melander M, Melander O, Metspalu A, Palmer CNA, Peters A, Rader DJ, Reilly MP, Loos RJF, Reiner AP, Roden DM, Tardif J-C, Thompson JR, Wareham NJ, Watkins H, Willer CJ, Samani NJ, Schunkert H, Deloukas P, Kathiresan S; Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease. J Am Coll Cardiol 2017;69:823-836.
35. Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J, Lu C, Smith NL, Uitterlinden AG, Roberts R, Khuseyinova N, Schnabel RB, Rice KM, Rivadeneira F, Hoogeveen RC, Fontes JD, Meisinger C, Keaney JF, Lemaitre R, Aulchenko YS, Vasan RS, Ellis S, Hazen SL, van Duijn CM, Nelson JJ, Marz W, Schunkert H, McPherson RM, Stirnadel-Farrant HA, Psaty BM, Gieger C, Siscovick D, Hofman A, Illig T, Cushman M, Yamamoto JF, Rotter JI, Larson MG, Stewart AFR, Boerwinkle E, Witteman JCM, Tracy RP, Koenig W, Benjamin EJ, Ballantyne CM. Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genomewide association studies from five community-based studies. Eur Heart J 2012;33: 238-251.
36. Major JM, Yu K, Wheeler W, Zhang H, Cornelis MC, Wright ME, Yeager M, Snyder K, Weinstein SJ, Mondul A, Eliassen H, Purdue M, Hazra A, McCarty CA, Hendrickson S, Virtamo J, Hunter D, Chanock S, Kraft P, Albanes D. Genomewide association study identifies common variants associated with circulating vitamin E levels. Hum Mol Genet 2011;20:3876-3883.
37. Manichaikul A, Naj AC, Herrington D, Post W, Rich SS, Rodriguez A. Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 2012;32:1991-1999.
38. Reboul E, Klein A, Bietrix F, Gleize B, Malezet-Desmoulins C, Schneider M, Margotat A, Lagrost L, Collet X, Borel P. Scavenger receptor class B type I (SRBI) is involved in vitamin E transport across the enterocyte. J Biol Chem 2006; 281:4739-4745.
39. Goti D, Reicher H, Malle E, Kostner GM, Panzenboeck U, Sattler W. High-density lipoprotein (HDL3)-associated alpha-tocopherol is taken up by HepG2 cells via the selective uptake pathway and resecreted with endogenously synthesized apo-lipoprotein B-rich lipoprotein particles. Biochem J 1998;332:57-65.
40. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, Marcel YL, Anderson RG, Mendelsohn ME, Hobbs HH, Shaul PW. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 2001;7:853-857.
41. Yesilaltay A, Kocher O, Pal R, Leiva A, Quinones V, Rigotti A, Krieger M. PDZK1 is required for maintaining hepatic scavenger receptor, class B, type I (SR-BI) steady state levels but not its surface localization or function. J Biol Chem 2006; 281:28975-28980.
42. Schäfer G, Guler R, Murray G, Brombacher F, Brown GD. The role of scavenger receptor B1 in infection with mycobacterium tuberculosis in a murine model. PLoS One 2009;4:e8448.
43. Vishnyakova TG, Kurlander R, Bocharov AV, Baranova IN, Chen Z, Abu-Asab MS, Tsokos M, Malide D, Basso F, Remaley A, Csako G, Eggerman TL, Patterson AP. CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells. Proc Natl Acad Sci USA 2006;103: 16888-16893.
44. Li X-A, Guo L, Dressman JL, Asmis R, Smart EJ. A novel ligand-independent apoptotic pathway induced by scavenger receptor class B, type I and suppressed by endothelial nitric-oxide synthase and high density lipoprotein. J Biol Chem 2005;280:19087-19096.
45. Stevens C, Avila BE, Neale BM, Kurki M, Ganna A, Graham D, Glaser B, Karczewski KJ, Minikel EV. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population. BioRxiv Prepr Serv Biol 2016;9: 1-37.
46. IBD Exomes Portal, Cambridge, MA (http://ibd.broadinstitute.org, accessed March 2018).