Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries
Open accessAbstract
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in 1 of 3 genes. In the 60% of patients who are mutation negative, we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL cholesterol (LDL-C)-raising alleles by use of a 12–single nucleotide polymorphism (12-SNP) score. The aims of the study were to improve the selection of SNPs and replicate the results in additional samples. METHODS: We used ROC curves to determine the optimum number of LDL-C SNPs. For replication analysis, we genotyped patients with a clinical diagnosis of FH from 6 countries for 6 LDL-C-associated alleles. We compared the weighted SNP score among patients with no confirmed mutation (FH/M–), those with a mutation (FH/M+), and controls from a UK population sample (WHII). RESULTS: Increasing the number of SNPs to 33 did not improve the ability of the score to discriminate between FH/M– and controls, whereas sequential removal of SNPs with smaller effects/lower frequency showed that a weighted score of 6 SNPs performed as well as the 12-SNP score. Metaanalysis of the weighted 6-SNP score, on the basis of polymorphisms in CELSR2 (cadherin, EGF LAG 7-pass G-type receptor 2), APOB (apolipoprotein B), ABCG5/8 [ATP-binding cassette, sub-family G (WHITE), member 5/8], LDLR (low density lipoprotein receptor), and APOE (apolipoprotein E) loci, in the independent FH/M– cohorts showed a consistently higher score in comparison to the WHII population (P < 2.2 × 10−16). Modeling in individuals with a 6-SNP score in the top three-fourths of the score distribution indicated a >95% likelihood of a polygenic explanation of their increased LDL-C. CONCLUSIONS: A 6-SNP LDL-C score consistently distinguishes FH/M– patients from healthy individuals. The hypercholesterolemia in 88% of mutation-negative patients is likely to have a polygenic basis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
With increasing knowledge, the importance of a polygenic background to familial hyperlipidaemias is emphasized.
“With increasing knowledge about common polymorphisms and lipoproteins, the importance of a polygenic background to familial hyperlipidaemias is emphasized. 67,122”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [122]
The importance of a polygenic background to familial hyperlipidaemias is emphasized with increasing knowledge.
“With increasing knowledge about common polymorphisms and lipoproteins, the importance of a polygenic background to familial hyperlipidaemias is emphasized.67,122”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [122]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Health inequalities among British civil servants: the Whitehall II study
Marmot, M. G., Stansfeld, S. A., Patel, C., North, F. M., Head, J. A., White, I. R., Brunner, E. J., Feeney, A., Marmot, M. G., & Smith, G. D. (1991) · The Lancet · doi:10.1016/0140-6736(91)93068-k · Cited by 3,571 · see citing works
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487 · see citing works
Self-citationNordestgaard, B. G., Chapman, M. J., Humphries, S. E., Ginsberg, H. N., Masana, L., Descamps, O. S., Wiklund, O., Hegele, R. A., Raal, F. J., Defesche, J. C., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht273 · Cited by 2,761 · see citing works
Self-citationEfficacy of statins in familial hypercholesterolaemia: a long term cohort study
Versmissen, J., Oosterveer, D. M., Yazdanpanah, M., Defesche, J. C., Basart, D. C. G., Liem, A. H., Heeringa, J., Witteman, J. C. M., Lansberg, P. J., Kastelein, J. J. P., et al. (2008) · BMJ · doi:10.1136/bmj.a2423 · Cited by 719 · see citing works
Self-citationBenn, M., Watts, G. F., Tybjaerg-Hansen, A., & Nordestgaard, B. G. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1563 · Cited by 632 · see citing works
Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients
Goldberg, A. C., Hopkins, P. N., Toth, P. P., Ballantyne, C. M., Rader, D. J., Robinson, J. G., Daniels, S. R., Gidding, S. S., de Ferranti, S. D., Ito, M. K., et al. (2011) · Journal of clinical lipidology · doi:10.1016/j.jacl.2011.03.001 · Cited by 622 · see citing works
Talmud, P. J., Shah, S. H., Whittall, R., Futema, M., Howard, P., Cooper, J. A., Harrison, S. C., Li, K., Drenos, F., Karpe, F., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62127-8 · Cited by 590 · see citing works
Self-citationA review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia
Marks, D., Thorogood, M., Neil, H. A. W., & Humphries, S. E. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(02)00330-1 · Cited by 569 · see citing works
Self-citationWilliams, R. R., Hunt, S. C., Schumacher, M. C., Hegele, R. A., Leppert, M. F., Ludwig, E. H., & Hopkins, P. N. (1993) · The American Journal of Cardiology · doi:10.1016/0002-9149(93)90155-6 · Cited by 566 · see citing works
Self-citationFamilial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients
Goldberg, A. C., Hopkins, P. N., Toth, P. P., Ballantyne, C. M., Rader, D. J., Robinson, J. G., Daniels, S. R., Gidding, S. S., de Ferranti, S. D., Ito, M. K., et al. (2011) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2011.04.003 · Cited by 545 · see citing works
Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands
Umans-Eckenhausen, M. A. W., Defesche, J. C., Sijbrands, E. J. G., Scheerder, R. L. J. M., & Kastelein, J. J. P. (2001) · The Lancet · doi:10.1016/s0140-6736(00)03587-x · Cited by 488 · see citing works
Self-citationSjouke, B., Kusters, D. M., Kindt, I., Besseling, J., Defesche, J. C., Sijbrands, E. J. G., van Lennep, J. E. R., Stalenhoef, A. F. H., Wiegman, A., Graaf, J. D., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu058 · Cited by 442 · see citing works
Self-citationFamilial hypercholesterolaemia: summary of NICE guidance
Wierzbicki, A. S., Humphries, S. E., Minhas, R., & on behalf of the Guideline Development Group (2008) · BMJ · doi:10.1136/bmj.a1095 · Cited by 237 · see citing works
Self-citationCost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia
Marks, D., Wonderling, D. E., Thorogood, M., Lambert, H., Humphries, S. E., & Neil, H. A. W. (2002) · BMJ · doi:10.1136/bmj.324.7349.1303 · Cited by 217 · see citing works
Self-citationFamilial hypercholesterolaemia: A model of care for Australasia
Watts, G. F., SULLIVAN, D. R., Poplawski, N. K., van Bockxmeer, F., Hamilton‐Craig, I. R., Clifton, P. M., O’Brien, R. C., Bishop, W., George, P. M., Barter, P. J., et al. (2011) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2011.06.001 · Cited by 205 · see citing works
Usifo, E., Leigh, S. E. A., Whittall, R., Lench, N., Taylor, A., Yeats, C., Orengo, C. A., Martin, A. C. R., Celli, J., & Humphries, S. E. (2012) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2012.00724.x · Cited by 201 · see citing works
Self-citationTaylor, A., Wang, D., Patel, K., Whittall, R., Wood, G. M., Farrer, M., Neely, R., Fairgrieve, S., Nair, D. R., Barbir, M., et al. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01356.x · Cited by 188 · see citing works
Self-citationAdemi, Z., Watts, G. F., Pang, J., Sijbrands, E. J. G., BOCKXMEER, F. M. V., O'Leary, P. C., Geelhoed, E. A., & Liew, D. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.05.008 · Cited by 173 · see citing works
Self-citationStarr, B. J., Hadfield, S. G., Hutten, B. A., Lansberg, P. J., Leren, T. P., Damgaard, D., Neil, H. A. W., & Humphries, S. E. (2008) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2008.135 · Cited by 165 · see citing works
Self-citationDescamps, O. S., Tenoutasse, S., Stéphenne, X., Gies, I., Beauloye, V., Lebrethon, M.-C., de Beaufort, C. E., Waele, K. D., Scheen, A. J., Rietzschel, E. R., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.06.016 · Cited by 149 · see citing works
Nherera, L. M., Marks, D., Minhas, R., Thorogood, M., & Humphries, S. E. (2011) · Heart · doi:10.1136/hrt.2010.213975 · Cited by 149 · see citing works
Self-citationTYBJARGHANSEN, A., & Humphries, S. E. (1992) · Atherosclerosis · doi:10.1016/0021-9150(92)90056-m · Cited by 146 · see citing works
Self-citationFutema, M., Plagnol, V., Li, K., Whittall, R., Neil, H. A. W., Seed, M., Bertolini, S., Calandra, S., Descamps, O. S., Graham, C. A., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102405 · Cited by 121 · see citing works
Self-citationHeath, K. E., Humphries, S. E., Middleton-Price, H. R., & Boxer, M. (2001) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200633 · Cited by 107 · see citing works
Self-citationFutema, M., Whittall, R., Kiley, A., Steel, L. K., Cooper, J. A., Badmus, E., Leigh, S. E. A., Karpe, F., Neil, H. A. W., & Humphries, S. E. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.04.011 · Cited by 94 · see citing works
Self-citationHuijgen, R., Kindt, I., Defesche, J. C., & Kastelein, J. J. P. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs038 · Cited by 78 · see citing works
Self-citationMarks, D., Thorogood, M., Neil, S., Humphries, S. E., & Neil, H. A. W. (2006) · Journal of Medical Screening · doi:10.1258/096914106778440617 · Cited by 69 · see citing works
Self-citationDatta, B. N., McDowell, I. F. W., & Rees, A. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833c14e2 · Cited by 51 · see citing works
Neil, H. A. W., Hawkins, M. M., Durrington, P. N., Betteridge, D. J., Capps, N. E., & Humphries, S. E. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.10.011 · Cited by 50 · see citing works
Self-citationSivapalaratnam, S., van Loendersloot, L. L., Hutten, B. A., Kastelein, J. J. P., Trip, M. D., & de Groot, E. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.06.040 · Cited by 21 · see citing works
Humphries, S. E. (2011) · Atherosclerosis Supplements · doi:10.1016/s1567-5688(11)00037-7 · Cited by 17 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw272 · Cited by 3,162 · see citing works
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.018 · Cited by 1,582 · see citing works
Clinical Genetic Testing for Familial Hypercholesterolemia
Sturm, A. C., Knowles, J. W., Gidding, S. S., Ahmad, Z., Ahmed, C. D., Ballantyne, C. M., Baum, S. J., Bourbon, M., Carrié, A., Cuchel, M., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.05.044 · Cited by 619 · see citing works
Self-citationFamilial hypercholesterolaemia
Defesche, J. C., Gidding, S. S., Harada‐Shiba, M., Hegele, R. A., Santos, R. D., & Wierzbicki, A. S. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.93 · Cited by 538 · see citing works
Self-citationSantos, R. D., Gidding, S. S., Hegele, R. A., Cuchel, M., Barter, P. J., Watts, G. F., Baum, S. J., Catapano, A. L., Chapman, M. J., Defesche, J. C., et al. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30041-9 · Cited by 423 · see citing works
Self-citationThe complex molecular genetics of familial hypercholesterolaemia
Berberich, A. J., & Hegele, R. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0052-6 · Cited by 298 · see citing works
Self-citationStatins for children with familial hypercholesterolemia
Vuorio, A. F., Kuoppala, J., Kovanen, P. T., Humphries, S. E., Tonstad, S., Wiegman, A., Drogari, E., & Ramaswami, U. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006401.pub4 · Cited by 265 · see citing works
Self-citationSevere hypertriglyceridemia is primarily polygenic
Dron, J. S., Wang, J., Cao, H., McIntyre, A. D., Iacocca, M. A., Menard, J. R., Movsesyan, I., Malloy, M. J., Pullinger, C. R., Kane, J. P., et al. (2019) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.10.006 · Cited by 222 · see citing works
Self-citationPolygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically
Wang, J., Dron, J. S., Ban, M. R., Robinson, J. F., McIntyre, A. D., Alazzam, M., Zhao, P., Dilliott, A. A., Cao, H., Huff, M. W., et al. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.308027 · Cited by 210 · see citing works
Self-citationFamilial hypercholesterolemia treatments: Guidelines and new therapies
Raal, F. J., Hovingh, G. K., & Catapano, A. L. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.859 · Cited by 198 · see citing works
Trinder, M., Li, X., DeCastro, M. L., Cermakova, L., Sadananda, S., Jackson, L. M., Azizi, H., Mancini, G. B. J., Francis, G. A., Frohlich, J. J., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.05.043 · Cited by 158 · see citing works
Universal Screening for Familial Hypercholesterolemia in Children
Klančar, G., Grošelj, U., Kovač, J., Bratanič, N., Bratina, N., Podkrajšek, K. T., & Battelino, T. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.07.017 · Cited by 152 · see citing works
Genetic testing in dyslipidemia: A scientific statement from the National Lipid Association
Brown, E. E., Sturm, A. C., Cuchel, M., Braun, L. T., Duell, P. B., Underberg, J. A., Jacobson, T. A., & Hegele, R. A. (2020) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2020.04.011 · Cited by 148 · see citing works
Self-citationGenetic and molecular architecture of familial hypercholesterolemia
Abifadel, M., & Boileau, C. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13577 · Cited by 145 · see citing works
Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018
Brunham, L. R., Ruel, I. L., Aljenedil, S., Rivière, J., Baass, A. W., Tu, J. V., Mancini, G. B. J., Raggi, P., Gupta, M., Couture, P., et al. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2018.09.005 · Cited by 138 · see citing works
Self-citationGrošelj, U., Kovač, J., Šuštar, U., Mlinarič, M., Fras, Z., Podkrajšek, K. T., & Battelino, T. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.858 · Cited by 118 · see citing works
Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes
Nanchen, D., Gencer, B., Müller, O., Auer, R., Aghlmandi, S., Heg, D., Klingenberg, R., Räber, L., Carballo, D., Carballo, S., et al. (2016) · Circulation · doi:10.1161/circulationaha.116.023007 · Cited by 114 · see citing works
Genetic Architecture of Familial Hypercholesterolaemia
Sharifi, M., Futema, M., Nair, D. R., & Humphries, S. E. (2017) · Current Cardiology Reports · doi:10.1007/s11886-017-0848-8 · Cited by 112 · see citing works
Self-citationGenetics of Familial Hypercholesterolemia: New Insights
Vrablı́k, M., Tichý, L., Freiberger, T., Blaha, V., Satny, M., & Hubacek, J. A. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.574474 · Cited by 113 · see citing works
Targeted next-generation sequencing in monogenic dyslipidemias
Hegele, R. A., Ban, M. R., Cao, H., McIntyre, A. D., Robinson, J. F., & Wang, J. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000163 · Cited by 106 · see citing works
Self-citationStatins for children with familial hypercholesterolemia
Vuorio, A. F., Kuoppala, J., Kovanen, P. T., Humphries, S. E., Tonstad, S., Wiegman, A., Drogari, E., & Ramaswami, U. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006401.pub5 · Cited by 104 · see citing works
Self-citationHumphries, S. E., Cooper, J. A., Seed, M., Capps, N. E., Durrington, P. N., Jones, B. J., McDowell, I. F. W., Soran, H., & Neil, H. A. W. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.04.040 · Cited by 94 · see citing works
Self-citationBrænne, I., Kleinecke, M., Reiz, B., Graf, E., Strom, T. M., Wieland, T., Fischer, M., Kessler, T., Hengstenberg, C., Meitinger, T., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.100 · Cited by 88 · see citing works
Hypercholesterolemia: The role of PCSK9
Melendez, Q. M., Krishnaji, S. T., Wooten, C. J., & Lopez, D. (2017) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2017.06.001 · Cited by 82 · see citing works
Familial hypercholesterolemia: A complex genetic disease with variable phenotypes
Taranto, M. D. D., Giacobbe, C., & Fortunato, G. (2019) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2019.103831 · Cited by 81 · see citing works
Self-citationSharifi, M., Higginson, E. J., Bos, S., Gallivan, A., Harvey, D., Li, K., Abeysekera, A., Haddon, A., Ashby, H. L., Shipman, K. E., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.05.015 · Cited by 78 · see citing works
Self-citationGenetics of Lipid and Lipoprotein Disorders and Traits
Dron, J. S., & Hegele, R. A. (2016) · Current Genetic Medicine Reports · doi:10.1007/s40142-016-0097-y · Cited by 76 · see citing works
Self-citationClinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia
Futema, M., Bourbon, M., Williams, M., & Humphries, S. E. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.006 · Cited by 73 · see citing works
Self-citationRecent advances in genetic testing for familial hypercholesterolemia
Iacocca, M. A., & Hegele, R. A. (2017) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2017.1332997 · Cited by 72 · see citing works
Self-citationPolygenic influences on dyslipidemias
Dron, J. S., & Hegele, R. A. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000482 · Cited by 72 · see citing works
Self-citationRamaswami, U., Futema, M., Bogsrud, M. P., Holven, K. B., van Lennep, J. E. R., Wiegman, A., Descamps, O. S., Vrablı́k, M., Freiberger, T., Dieplinger, H., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.11.012 · Cited by 69 · see citing works
Self-citationPolygenic Hypercholesterolemia and Cardiovascular Disease Risk
Sharifi, M., Futema, M., Nair, D. R., & Humphries, S. E. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1130-z · Cited by 68 · see citing works
Self-citationTrinder, M., Paquette, M., Cermakova, L., Ban, M. R., Hegele, R. A., Baass, A. W., & Brunham, L. R. (2020) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.120.002919 · Cited by 65 · see citing works
Self-citationPolygenic link between blood lipids and amyotrophic lateral sclerosis
Chen, X., Yazdani, S., Piehl, F., Magnusson, P. K. E., & Fang, F. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.03.022 · Cited by 63 · see citing works
Ellis, K. L., Pang, J., Chan, D. C., Hooper, A. J., Bell, D. A., Burnett, J. R., & Watts, G. F. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.08.011 · Cited by 57 · see citing works
Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management
Mytilinaiou, M. G., Kyrou, I., Khan, M., Grammatopoulos, D. K., & Randeva, H. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00707 · Cited by 59 · see citing works
The evolution of genetic-based risk scores for lipids and cardiovascular disease
Dron, J. S., & Hegele, R. A. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000576 · Cited by 58 · see citing works
Self-citationManagement of Familial Hypercholesterolemia: Current Status and Future Perspectives
Lui, D. T. W., Lee, A. C. H., & Tan, K. C. B. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa122 · Cited by 56 · see citing works
The UK Paediatric Familial Hypercholesterolaemia Register: preliminary data
Ramaswami, U., Cooper, J. A., & Humphries, S. E. (2016) · Archives of Disease in Childhood · doi:10.1136/archdischild-2015-308570 · Cited by 53 · see citing works
Self-citationGenetic testing for familial hypercholesterolemia—past, present, and future
Futema, M., Taylor-Beadling, A., Williams, M., & Humphries, S. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100139 · Cited by 50 · see citing works
Self-citationHumphries, S. E., Cooper, J. A., Dale, P., & Ramaswami, U. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.11.005 · Cited by 49 · see citing works
Self-citationLee, S., Akioyamen, L. E., Aljenedil, S., Rivière, J., Ruel, I. L., & Genest, J. J. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319829746 · Cited by 44 · see citing works
My Approach to the Patient With Familial Hypercholesterolemia
Safarova, M. S., & Kullo, I. J. (2016) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2016.04.013 · Cited by 42 · see citing works
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I. M., Backer, G. D., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Kardiologia Polska · doi:10.5603/kp.2016.0157 · Cited by 41 · see citing works
Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women
Balder, J.-W., Rimbert, A., Zhang, X., Viel, M., Kanninga, R., van Dijk, F., Lansberg, P. J., Sinke, R. J., & Kuivenhoven, J. A. (2018) · Circulation · doi:10.1161/circulationaha.117.032479 · Cited by 42 · see citing works
Contribution of <i>APOE</i> Genetic Variants to Dyslipidemia
Bea, A. M., Larrea-Sebal, A., Marco-Benedi, V., Uribe, K. B., Galicia-Garcia, U., Lamiquiz-Moneo, I., Laclaustra, M., Moreno-Franco, B., Fernandez-Corredoira, P., Olmos, S., et al. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.123.318977 · Cited by 40 · see citing works
Corella, D., Coltell, Ó., Mattingley, G., Sorlí, J. V., & Ordovás, J. M. (2017) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2017.1311208 · Cited by 40 · see citing works
Genetic basis of hypercholesterolemia in adults
Saadatagah, S., Jose, M. T., Dikilitas, O., Alhalabi, L., Miller, A. A., Fan, X., Olson, J. E., Kochan, D. C., Safarova, M. S., & Kullo, I. J. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00190-z · Cited by 40 · see citing works
Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis
Taranto, M. D. D., & Fortunato, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043224 · Cited by 40 · see citing works
Self-citationStanciulescu, L. A., Scafa‐Udriște, A., & Dorobanţu, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076669 · Cited by 43 · see citing works
D’Erasmo, L., Minicocci, I., Costanzo, A. D., Pigna, G., Commodari, D., Ceci, F., Montali, A., Brancato, F., Stanca, I., Nicolucci, A., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.018932 · Cited by 39 · see citing works
Futema, M., Ramaswami, U., Tichý, L., Bogsrud, M. P., Holven, K. B., van Lennep, J. E. R., Wiegman, A., Descamps, O. S., Leener, A. D., Fastré, E., et al. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.01.008 · Cited by 37 · see citing works
Self-citationDyslipidemias in clinical practice
Cabezas, M. C., Burggraaf, B., & Klop, B. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.09.010 · Cited by 36 · see citing works
The genetic spectrum of familial hypercholesterolemia in south-eastern Poland
Sharifi, M., Waluś‐Miarka, M., Idzior−Waluś, B., Malecki, M. T., Sanak, M., Whittall, R., Li, K., Futema, M., & Humphries, S. E. (2015) · Metabolism · doi:10.1016/j.metabol.2015.10.018 · Cited by 34 · see citing works
Self-citationTaranto, M. D. D., D'Agostino, M. N., & Fortunato, G. (2015) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2015.06.007 · Cited by 33 · see citing works
Self-citationProgress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism
Ellis, K. L., Hooper, A. J., Burnett, J. R., & Watts, G. F. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.69 · Cited by 33 · see citing works
Taranto, M. D. D., Giacobbe, C., Palma, D., Iannuzzo, G., Gentile, M., Calcaterra, I. L., Guardamagna, O., Auricchio, R., Minno, M. N. D. D., & Fortunato, G. (2021) · Clinical Genetics · doi:10.1111/cge.14036 · Cited by 32 · see citing works
Self-citationAre Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?
Paynter, N. P., Ridker, P. M., & Chasman, D. I. (2016) · Circulation Research · doi:10.1161/circresaha.115.306360 · Cited by 31 · see citing works
Mariano, C., Alves, A. C., Medeiros, A. M., Chora, J. R., Antunes, M. C. D. S., Futema, M., Humphries, S. E., & Bourbon, M. (2019) · Clinical Genetics · doi:10.1111/cge.13697 · Cited by 30 · see citing works
Self-citationDiagnostic scoring for familial hypercholesterolaemia in practice
Haralambos, K., Ashfield-Watt, P. A. L., & McDowell, I. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000325 · Cited by 29 · see citing works
Masana, L., Ibarretxe, D., Rodríguez-Borjabad, C., Plana, N., Valdivielso, P., Pedro‐Botet, J., Civeira, F., López‐Miranda, J., Guijarro, C., Mostaza, J. M., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.06.905 · Cited by 28 · see citing works
Iyen, B., Qureshi, N., Kai, J., Akyea, R. K., Leonardi‐Bee, J., Roderick, P. J., Humphries, S. E., & Weng, S. F. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.05.017 · Cited by 28 · see citing works
Self-citationPek, S. L. T., Dissanayake, S., Fong, J. C. W., Lin, M. X., Chan, E. Z. L., Tang, J. I.-S., Lee, C. W., Ong, H. Y., Sum, C. F., Lim, S. C., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.12.028 · Cited by 27 · see citing works
Hooper, A. J., Burnett, J. R., Bell, D. A., & Watts, G. F. (2018) · Current Atherosclerosis Reports · doi:10.1007/s11883-018-0731-0 · Cited by 27 · see citing works
Medeiros, A. M., Alves, A. C., Miranda, B., Chora, J. R., Bourbon, M., Bourbon, M., Rato, Q., Alves, A. C., Medeiros, A. M., Gomes, A. C., et al. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100490 · Cited by 25 · see citing works
Page, M. M., Stefanutti, C., Sniderman, A. D., & Watts, G. F. (2015) · Clinical Science · doi:10.1042/cs20140755 · Cited by 25 · see citing works
Futema, M., Cooper, J. A., Charakida, M., Boustred, C. R., Sattar, N. A., Deanfield, J. E., Lawlor, D. A., Timpson, N. J., Humphries, S. E., & Hingorani, A. D. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.03.007 · Cited by 25 · see citing works
Self-citationWiegman, A., Bourbon, M., Freiberger, T., Gidding, S. S., Greber‐Platzer, S., Grošelj, U., Holven, K. B., Hudgins, L. C., Humphries, S. E., Hutten, B. A., et al. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag382 · Cited by 24 · see citing works
Self-citationChildren with hypercholesterolemia of unknown cause: Value of genetic risk scores
Sjouke, B., Tanck, M. W. T., Fouchier, S. W., Defesche, J. C., Hutten, B. A., Wiegman, A., Kastelein, J. J. P., & Hovingh, G. K. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.02.017 · Cited by 24 · see citing works
Self-citationAnalysis of Children and Adolescents with Familial Hypercholesterolemia
Minicocci, I., Pozzessere, S., Prisco, C., Montali, A., Costanzo, A. D., Martino, E., Martino, F., & Arca, M. (2017) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.12.075 · Cited by 24 · see citing works
Marco-Benedí, V., Cenarro, A., Laclaustra, M., Larrea, A., Jarauta, E., Lamíquiz-Moneo, I., Calmarza, P., Bea, A. M., Plana, N., Pintó, X., et al. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.08.009 · Cited by 24 · see citing works
Familial hypercholesterolemia: experience from France
Rabès, J., Béliard, S., & Carrié, A. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000496 · Cited by 24 · see citing works
Atualização da Diretriz Brasileira de Hipercolesterolemia Familiar – 2021
Izar, M. C. D. O., Rocha, V. Z., Bertolami, A., Santos, R. D., Lottenberg, A. M., Assad, M. H. V., Saraiva, J. F. K., Chacra, A. P. M., Martinez, T. L. D. R., Bahia, L., et al. (2021) · Arquivos Brasileiros de Cardiologia · doi:10.36660/abc.20210788 · Cited by 31 · see citing works
Fahed, A. C., Khalaf, R. I., Salloum, R. H., Andary, R. R., Safa, R., El‐Rassy, I., Moubarak, E. M., Azar, S. T., Bitar, F. F., & Nemer, G. M. (2016) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.203 · Cited by 23 · see citing works
Ghaleb, Y., Elbitar, S., Khoury, P. E., Bruckert, É., Carreau, V., Carrié, A., Moulin, P., Filippo, M. D., Charrière, S., Iliozer, H., et al. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-017-0078-y · Cited by 23 · see citing works
Séguro, F., Rabès, J., Taraszkiewicz, D., Ruidavets, J., Bongard, V., & Ferrières, J. (2018) · Clinical Cardiology · doi:10.1002/clc.22881 · Cited by 23 · see citing works
Radoviča-Spalviņa, I., Latkovskis, G., Silamiķelis, I., Frīdmanis, D., Elbere, I., Ventiņš, K., Ozola, G., Ērglis, A., & Kloviņš, J. (2015) · BMC Medical Genetics · doi:10.1186/s12881-015-0230-x · Cited by 22 · see citing works
Efficacy of clinical diagnostic criteria for familial hypercholesterolemia genetic testing in Poland
Mickiewicz, A., Chmara, M., Futema, M., Fijałkowski, M., Chlebus, K., Gałąska, R., Bandurski, T., Pajkowski, M., Żuk, M., Wasąg, B., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.03.025 · Cited by 22 · see citing works
Self-citationMolecular genetics of familial hypercholesterolemia in Israel–revisited
Durst, R. Y., Ibe, U. K., Shpitzen, S., Schurr, D., Eliav, O., Futema, M., Whittall, R., Szalat, A., Meiner, V., Knobler, H., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.12.021 · Cited by 23 · see citing works
Self-citationBlanco‐Vaca, F., Martín-Campos, J. M., Beteta-Vicente, Á., Canyelles, M., Martínez, S., Roig, R., Farré, N., Julve, J., & Tondo, M. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.01.036 · Cited by 22 · see citing works
Taranto, M. D. D., de Falco, R., Guardamagna, O., Massini, G., Giacobbe, C., Auricchio, R., Malamisura, B., Proto, M., Palma, D., Greco, L., et al. (2019) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2018-1037 · Cited by 21 · see citing works
Self-citationPirazzi, C., Håkansson, L., Gustafsson, C., Ömerovic, E., Wiklund, O., & Mancina, R. M. (2019) · The Application of Clinical Genetics · doi:10.2147/tacg.s202942 · Cited by 21 · see citing works
Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia
Rieck, L., Bardey, F., Grenkowitz, T., Bertram, L., Helmuth, J., Mischung, C., Spranger, J., Steinhagen‐Thiessen, E., Bobbert, T., Kassner, U., et al. (2020) · Clinical Genetics · doi:10.1111/cge.13826 · Cited by 21 · see citing works
Семенова, А. Е., Сергиенко, И. В., García-Giustiniani, D. A., Monserrat, L., Попова, А. Б., Нозадзе, Д. Н., & Владиславович, Е. М. (2020) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd7020016 · Cited by 20 · see citing works
Jacob, E. O., & Hegele, R. A. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01018-6 · Cited by 19 · see citing works
Self-citationVanhoye, X., Bardel, C., Rimbert, A., Moulin, P., Rollat‐Farnier, P., Muntaner, M., Marmontel, O., Dumont, S., Charrière, S., Cornélis, F., et al. (2022) · Translational research · doi:10.1016/j.trsl.2022.12.002 · Cited by 19 · see citing works
Aortic Calcification Progression in Heterozygote Familial Hypercholesterolemia
Al-Kindi, M., Bélanger, A. M., Sayegh, K., Senouci, S. I., Aljenedil, S., Sivakumaran, L., Ruel, I. L., Al‐Rasadi, K., Waili, K. A., Awan, Z. A., et al. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.02.001 · Cited by 18 · see citing works
Phenotype vs. genotype in severe familial hypercholesterolemia: what matters most for the clinician?
Santos, R. D. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000391 · Cited by 18 · see citing works
Molecular diagnosis of familial hypercholesterolaemia
Graham, C. A., Latten, M. J., & Hart, P. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000430 · Cited by 18 · see citing works
Improving the detection of familial hypercholesterolaemia
Lan, N. S. R., Martin, A. C., Brett, T., Watts, G. F., & Bell, D. A. (2018) · Pathology · doi:10.1016/j.pathol.2018.10.015 · Cited by 18 · see citing works
Jiang, L., Wu, W., Sun, L., Chen, P., Wang, W., Benito‐Vicente, A., Zhang, F., Pan, X.-D., Cui, W., Yang, S., et al. (2016) · Scientific Reports · doi:10.1038/srep36823 · Cited by 17 · see citing works
Improving the cost-effectiveness equation of cascade testing for familial hypercholesterolaemia
Pears, R., Griffin, M., Futema, M., & Humphries, S. E. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000173 · Cited by 17 · see citing works
Self-citationBeyond the Usual Suspects: Expanding on Mutations and Detection for Familial Hypercholesterolemia
Ibrahim, S., Defesche, J. C., & Kastelein, J. J. P. (2021) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2021.1953985 · Cited by 15 · see citing works
Self-citationGenotype-guided diagnosis in familial hypercholesterolemia: clinical management and concerns
Hopkins, P. N., & Lane, S. R. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000397 · Cited by 15 · see citing works
Martín-Campos, J. M., Plana, N., Figueras, R., Ibarretxe, D., Caixàs, A., Esteve, E., Pérez, A., Bueno, M., Mauri, M., Roig, R., et al. (2018) · Journal of clinical lipidology · doi:10.1016/j.jacl.2018.09.002 · Cited by 15 · see citing works
Nor, N. S. M., Al-Khateeb, A. M., Chua, Y.-A., Kasim, N. A. M., & Nawawi, H. M. (2019) · BMC Pediatrics · doi:10.1186/s12887-019-1474-y · Cited by 15 · see citing works
Teng, M., Yeh, K.-H., Hsu, L., Chou, H., Er, L., Wu, S., & Ko, Y. (2023) · Genes · doi:10.3390/genes14030754 · Cited by 14 · see citing works
Mickiewicz, A., Futema, M., Ćwiklińska, A., Kuchta, A., Jankowski, M., Kaszubowski, M. F., Chmara, M., Wasąg, B., Fijałkowski, M., Jaguszewski, M. J., et al. (2020) · Life · doi:10.3390/life10050073 · Cited by 14 · see citing works
Self-citationCatapano, F., Galea, N., Pambianchi, G., D’Erasmo, L., Borrazzo, C., Cundari, G., Marchitelli, L., Maranghi, M., Minicocci, I., Costanzo, A. D., et al. (2023) · La radiologia medica · doi:10.1007/s11547-023-01610-z · Cited by 14 · see citing works
Mollaki, V., & Drogari, E. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.02.020 · Cited by 14 · see citing works
Self-citation
- Authors
- Futema, M., Shah, S., Cooper, J. A., Li, K., Whittall, R. A., Sharifi, M., Goldberg, O., Drogari, E., Mollaki, V., Wiegman, A., Defesche, J., D'Agostino, M. N., D'Angelo, A., Rubba, P., Fortunato, G., Waluś-Miarka, M., Hegele, R. A., Aderayo Bamimore, M., Durst, R., Leitersdorf, E., Mulder, M. T., Roeters van Lennep, J. E., Sijbrands, E. J. G., Whittaker, J. C., Talmud, P. J., & Humphries, S. E.
- Affiliations
- British Heart Foundation (GB)
- The University of Queensland (AU)
- National and Kapodistrian University of Athens (GR)
- Department of Pediatrics and
- Amsterdam UMC Location University of Amsterdam (NL)
- CEINGE S.C.a r.l. Advanced Biotechnology, Naples, Italy
- Federico II University Hospital (IT)
- CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
- Department of Metabolic Diseases and Department of Medical Didactics, Jagiellonian University Medical College, Krakow, Poland
- Robarts Research Institute (CA)
- Robarts Research Institute, London, Ontario, Canada
- Hadassah Medical Center (IL)
- Erasmus MC (NL)
- Departments of Cardiology and Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Humphries, Steve E
- ORCID
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-01-01
- Volume
- 61
- Issue
- 1
- Pages
- 231-238
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC4892342
- OpenAlex
- W2109770394
- Cited by
- 213
- References
- 32
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 11 · 2023: 13 · 2022: 21 · 2021: 15 · 2020: 13 · 2019: 27 · 2018: 24 · 2017: 26 · 2016: 24 · 2015: 13 · 2014: 1
- FWCI
- 21.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Medical Research Council
- British Heart Foundation
- Health and Safety Executive
- Department of Health Research
- National Heart, Lung, and Blood Institute (HL36310)
- National Institute on Aging (AG13196)
- Agency for Health Care Policy and Research (HS06516)
- British Heart Foundation BHF (PG08/008)
- National Institute for Health Research
- University College London
- Athens University of Economics and Business
- Netherlands Heart Foundation (2006B190)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- familial hypercholesterolemia, LDL cholesterol, polygenic risk score, single nucleotide polymorphisms, polygenic hypercholesterolemia, LDL receptor, apolipoprotein B, ABCG5/8, apolipoprotein E, CELSR2, genetic risk prediction, replication
- MeSH terms
- Proprotein Convertase 9, Adolescent, Adult, Alleles, Apolipoproteins B, Canada, Child, Europe, Female, Humans, Hyperlipoproteinemia Type II, Israel, Cholesterol, LDL, Male, Middle Aged, Mutation, Receptors, LDL, Risk Factors, ROC Curve, Serine Endopeptidases, Cohort Studies, Case-Control Studies, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Proprotein Convertases, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
