Heritability of apolipoprotein (a) traits in two-generational African-American and Caucasian families

Heritability of LPA allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6–74 years). We determined: 1) Lp(a) levels; 2) LPA allele sizes; 3) apo(a) isoform sizes; and 4) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis. The ethnicity-adjusted heritability estimate for Lp(a) level was 0.95. Heritability for ISLs corresponding to the smaller LPA allele in a given allele-pair was higher than that corresponding to the larger LPA allele (0.91 vs. 0.59, P = 0.017). Although not statistically different, heritability for both apo(a) isoforms (0.90 vs. 0.70) and LPA alleles (0.98 vs. 0.82) was higher for the smaller versus larger sizes. Heritability was generally lower in African-Americans versus Caucasians with a 4-fold difference for the larger LPA allele (0.25 vs. 0.94, P = 0.001). In Caucasians, an overall higher heritability pattern was noted for the older (≥47 years) versus younger (<47 years) families. In conclusion, Lp(a) level and traits associated with the smaller LPA alleles were strongly determined by genetics, although with a varying ethnic influence. Ethnic differences in heritability of the larger LPA allele warrant further investigations. Heritability of LPA allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6–74 years). We determined: 1) Lp(a) levels; 2) LPA allele sizes; 3) apo(a) isoform sizes; and 4) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis. The ethnicity-adjusted heritability estimate for Lp(a) level was 0.95. Heritability for ISLs corresponding to the smaller LPA allele in a given allele-pair was higher than that corresponding to the larger LPA allele (0.91 vs. 0.59, P = 0.017). Although not statistically different, heritability for both apo(a) isoforms (0.90 vs. 0.70) and LPA alleles (0.98 vs. 0.82) was higher for the smaller versus larger sizes. Heritability was generally lower in African-Americans versus Caucasians with a 4-fold difference for the larger LPA allele (0.25 vs. 0.94, P = 0.001). In Caucasians, an overall higher heritability pattern was noted for the older (≥47 years) versus younger (<47 years) families. In conclusion, Lp(a) level and traits associated with the smaller LPA alleles were strongly determined by genetics, although with a varying ethnic influence. Ethnic differences in heritability of the larger LPA allele warrant further investigations. Lipoprotein(a) [Lp(a)], a major genetic cardiovascular risk factor, consists of a LDL-like particle and a unique apolipoprotein, i.e., apo(a), linked to the apoB-100 via a single disulfide bond (1Enkhmaa B. Anuurad E. Zhang W. Berglund L. Lipoprotein(a). In Dyslipidemias: Pathophysiology, Evaluation and Management. P. M. Conn and A. Garg, editors. Springer Science & Business Media, LLC. Chicago, IL2015: 25-55Google Scholar). Although stable intra-individually, Lp(a) levels vary substantially between individuals and ethnicities. On average, populations of African descent exhibit 2- to 3-fold higher Lp(a) levels compared with populations of European descent (1Enkhmaa B. Anuurad E. Zhang W. Berglund L. Lipoprotein(a). In Dyslipidemias: Pathophysiology, Evaluation and Management. P. M. Conn and A. Garg, editors. Springer Science & Business Media, LLC. Chicago, IL2015: 25-55Google Scholar, 2Sandholzer C. Hallman D.M. Saha N. Sigurdsson G. Lackner C. Csaszar A. Boerwinkle E. Utermann G. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups.Hum. Genet. 1991; 86: 607-614Crossref PubMed Scopus (349) Google Scholar, 3Scholz M. Kraft H.G. Lingenhel A. Delport R. Vorster E.H. Bickeboller H. Utermann G. Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians.Eur. J. Hum. Genet. 1999; 7: 169-178Crossref PubMed Scopus (55) Google Scholar). Twin-pairs and family studies report a consistently high heritability estimate for Lp(a) level, making Lp(a) one of the most heritable quantitative human traits (4Kraft H.G. Kochl S. Menzel H.J. Sandholzer C. Utermann G. The apolipoprotein (a) gene: a transcribed hypervariable locus controlling plasma lipoprotein (a) concentration.Hum. Genet. 1992; 90: 220-230Crossref PubMed Scopus (229) Google Scholar, 5Austin M.A. Sandholzer C. Selby J.V. Newman B. Krauss R.M. Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes.Am. J. Hum. Genet. 1992; 51: 829-840PubMed Google Scholar, 6Hong Y. Dahlen G.H. Pedersen N. Heller D.A. McClearn G.E. de Faire U. Potential environmental effects on adult lipoprotein(a) levels: results from Swedish twins.Atherosclerosis. 1995; 117: 295-304Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 7Abney M. McPeek M.S. Ober C. Broad and narrow heritabilities of quantitative traits in a founder population.Am. J. Hum. Genet. 2001; 68: 1302-1307Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 8Mooser V. Scheer D. Marcovina S.M. Wang J. Guerra R. Cohen J. Hobbs H.H. The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans.Am. J. Hum. Genet. 1997; 61: 402-417Abstract Full Text PDF PubMed Scopus (86) Google Scholar). Population-based studies have uniformly demonstrated an inverse association of the number of kringle 4 (K4) type 2 repeats with Lp(a) level across ethnic groups (2Sandholzer C. Hallman D.M. Saha N. Sigurdsson G. Lackner C. Csaszar A. Boerwinkle E. Utermann G. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups.Hum. Genet. 1991; 86: 607-614Crossref PubMed Scopus (349) Google Scholar, 3Scholz M. Kraft H.G. Lingenhel A. Delport R. Vorster E.H. Bickeboller H. Utermann G. Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians.Eur. J. Hum. Genet. 1999; 7: 169-178Crossref PubMed Scopus (55) Google Scholar, 4Kraft H.G. Kochl S. Menzel H.J. Sandholzer C. Utermann G. The apolipoprotein (a) gene: a transcribed hypervariable locus controlling plasma lipoprotein (a) concentration.Hum. Genet. 1992; 90: 220-230Crossref PubMed Scopus (229) Google Scholar, 8Mooser V. Scheer D. Marcovina S.M. Wang J. Guerra R. 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Utermann G. of apolipoprotein(a) kringle alleles and effects on lipoprotein(a) levels in and African the of alleles is J. Hum. Genet. PubMed Scopus Google Scholar, S.M. P. concentrations and in Caucasians and African The Thromb. PubMed Scopus Google Scholar, S. C.H. Apolipoprotein kringle 4 polymorphism and lipoprotein (a) concentrations in African Biol. Google Scholar). a lower heritability estimate for Lp(a) level in Africans versus the LPA locus almost of the genetic of the Lp(a) in Caucasians, for of the in Africans M. Kraft H.G. Lingenhel A. Delport R. Vorster E.H. Bickeboller H. Utermann G. Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians.Eur. J. Hum. Genet. 1999; 7: 169-178Crossref PubMed Scopus (55) Google Scholar). In to the size genetic the LPA and to differences in levels C. D. A. E. N. in LPA most of the variation in Lp(a) levels in African PubMed Scopus Google Scholar). a was for Lp(a) African-Americans and Marcovina S.M. D. E. M. of lipoprotein(a) in African Americans and for a 1997; PubMed Scopus Google Scholar). Although studies have an as as a L. Ober C. M. Heritability of effects on human quantitative PubMed Scopus Google the of as the of in Lp(a) heritability to the LPA allele size plasma Lp(a) in most individuals consists of two particle populations with different apo(a) sizes. the heritability of vs. LPA of a given allele-pair across families of different ethnic In the heritability of traits and isoform-specific apo(a) levels in a of African-Americans and Caucasians and determined heritability We the effects of LPA to in both ethnic groups on the The of human and for families have B. Anuurad E. Zhang W. Berglund L. of versus in Caucasians and Full Text Full Text PDF PubMed Scopus Google Scholar). 82 Caucasian and families with two parents and two children were from the in the greater were to the of and Science for of and and was for individual family on families were as Caucasian from two children in ethnic and one Caucasian were not to of and the report is on the in Caucasians and The was by the the of in with the of and was from were to for of for and one of the parents the for was with a was as by of children and for for and were to a of and were concentrations were with the of and of the concentration of lipoprotein in of the PubMed Scopus Google Scholar). Lp(a) levels were determined with an in plasma were to the in with two different were the for LPA allele were determined by of from in with a from Lackner C. Boerwinkle E. Leffert C.C. Hobbs H.H. of apolipoprotein (a) isoform size as by Clin. Invest. 1991; PubMed Scopus Google and J. Paultre F. Tuck C.H. Holleran S. Reed R.G. Pearson T.A. Thomas C.M. Ramakrishnan R. Berglund L. Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.J. Lipid Full Text Full Text PDF PubMed Google as Apo(a) isoform were determined by with of plasma by a of and hypervariable polymorphism of apolipoprotein J. Hum. Genet. 1991; Google Scholar). apo(a) were with the The results were to human apo(a) isoform with apo(a) isoforms the inverse between the number of repeats and isoform The isoform dominance pattern was by of the apo(a) on the by a of as J. Paultre F. Tuck C.H. Holleran S. Reed R.G. Pearson T.A. Thomas C.M. Ramakrishnan R. Berglund L. Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.J. Lipid Full Text Full Text PDF PubMed Google Scholar, B. Anuurad E. Zhang W. Li Berglund L. The of apo(a) and dominance pattern in in Lp(a) with Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). Lp(a) levels were to the of of the on the as in B. Anuurad E. Zhang W. Abbuthalha A. Li X.D. Dotterweich W. Pollard R.B. Asmuth D.M. Berglund L. HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels.Arterioscler. Thromb. Vasc. Biol. 2013; 33: 387-392Crossref PubMed Scopus (23) Google Scholar, B. Anuurad E. Zhang W. Li Berglund L. The of apo(a) and dominance pattern in in Lp(a) with Lipid Full Text Full Text PDF PubMed Scopus Google Scholar, F. Pearson T.A. Tuck C.H. M. J. Reed R.G. levels of Lp(a) with a apo(a) isoform associated with coronary artery disease in African and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). for were by and of were for the of of were for LPA a on a the of the and from The of an and were with the and genotype were the in the LPA were the allele was greater than and than in both African and The The the were by and were by of were with were as of with for Lp(a) and isoform-associated Lp(a) level for larger smaller were to analysis. differences were determined by Heritability of was estimated by the of the of on the of on in families of with two with and as a for ethnicity-adjusted and for one family the was the was on the and the was heritability between and in differences in heritability were by and families. family the of parents was for and the of was determined years). were younger the of parents was older the of parents was association for were association X. M. for association Genet. PubMed Scopus Google a control was by the parents and two in in from to were than The of was and for African-Americans and Caucasians, The of parents was and 7 for African-Americans and Caucasians, were differences parents for and levels were lower in African-Americans versus Caucasians for both and parents = In the concentration was higher in African-American compared with Caucasian = the Lp(a) level was 3-fold higher in both African-American and parents compared with Caucasian and vs. P for vs. 7 P 0.001). both ISLs corresponding to the smaller larger apo(a) were in African-Americans versus Caucasians for both parents and for ethnic were for LPA allele sizes, in a of for LPA in the of the smaller apo(a) in in an apo(a) the corresponding for the larger apo(a) was an between the of LPA alleles and apo(a) isoforms was for the smaller in both ethnic In different were for the larger sizes. Caucasian the LPA allele and apo(a) isoform were and The for the larger and smaller LPA alleles were between African-Americans and of = = = = 7 versus Caucasian versus Caucasian apoB-100 versus Caucasian Lp(a) level versus Caucasian versus Caucasian larger versus Caucasian versus Caucasian smaller versus Caucasian versus Caucasian apo(a) larger apo(a) smaller as for associated with the larger allele in a given LPA associated with the smaller allele in a given LPA P versus Caucasian P versus Caucasian P versus Caucasian in a as for associated with the larger allele in a given LPA associated with the smaller allele in a given LPA The ethnicity-adjusted overall heritability estimate for the Lp(a) level was that of individual differences in Lp(a) level were to Lp(a) heritability was by apo(a) size the heritability of the isoform-specific Lp(a) level corresponding to smaller larger apo(a) size a given the heritability estimate of the isoform-specific Lp(a) level for the smaller apo(a) size was greater than that corresponding to the larger apo(a) size vs. P = for (0.91 vs. 0.59, P = 0.017). difference was for LPA We estimated the heritability for and compared between Caucasians and In Caucasians, traits were heritable P In isoform-specific levels for both apo(a) as as smaller isoform and allele were heritable P heritability was for the larger allele and isoform in Although heritability was generally lower in African-Americans versus Caucasians, differences were for ISLs apo(a) isoforms between two ethnicities. In a 4-fold lower heritability in African-Americans versus Caucasians was for the larger LPA allele (0.25 vs. 0.94, P = 0.001). the heritability in African-Americans to 3-fold higher from for Lp(a) and traits in families and for for for differences between associated with larger versus smaller apo(a) for differences between associated with larger versus smaller apo(a) Lp(a) with LPA alleles that not to apo(a) i.e., were not in the isoform isoform genotype allele allele heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA for differences between associated with larger versus smaller apo(a) with LPA alleles that not to apo(a) i.e., were not in the in a from for Lp(a) and traits by for Ethnic with LPA alleles that not to apo(a) i.e., were not in the with LPA alleles that not to apo(a) i.e., were not in the allele, allele, heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA with LPA alleles that not to apo(a) i.e., were not in the in a heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA We families two groups on the of parents in the years) and compared heritability for younger (<47 years) versus older (≥47 years) families to heritability by of family were differences in of between Caucasians and African-Americans for younger 4 vs. 4 older vs. families. In Caucasians, traits were heritable in both groups P Although not different, heritability were consistently higher in older versus younger Caucasian families for In the heritability pattern was Heritability were lower for larger LPA allele and apo(a) isoform sizes, not for in older versus younger families the heritability estimate of the Lp(a) level was lower in older versus younger African-American families vs. P In younger heritability not between Caucasians and African-Americans In in older effects on heritability between Caucasians and African-Americans for Lp(a) level and the larger LPA allele both heritability was lower in African-Americans versus Caucasians vs. P for ethnic the larger LPA allele vs. P for ethnic heritability of Lp(a) and (<47 (≥47 (<47 (≥47 for ethnic difference vs. for difference between younger versus older with LPA alleles that not to apo(a) i.e., were not in the with LPA alleles that not to apo(a) i.e., were not in the allele, for ethnic difference vs. allele, years) of in the was to families to younger and older heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA P for ethnic difference vs. P for difference between younger versus older with LPA alleles that not to apo(a) i.e., were not in the P for ethnic difference vs. in a The years) of in the was to families to younger and older heritability associated with the larger allele in a given LPA associated with the smaller allele in a given LPA In to LPA genetic associated with isoform-associated Lp(a) level for smaller and larger apo(a) an association analysis. of LPA in the were associated with Lp(a) level for smaller larger apo(a) although were not In Caucasians, were as associated with Lp(a) level, the allele associated with a level of and were to associated with ISLs for smaller and larger apo(a) sizes, the allele associated with in the levels of was associated with of the in in a different of of was to associated with the of and the on both Lp(a) level and for smaller apo(a) sizes. ethnic that effects were of level, for for and the not In family the heritability of isoform-specific Lp(a) level for apo(a) size as as larger and smaller LPA alleles and apo(a) isoforms in to and In to the heritable of the Lp(a) level, demonstrated that traits associated with the smaller apo(a) size of a given allele-pair the most determined heritable quantitative human a higher of in by for the smaller versus larger apo(a) sizes. Although demonstrated differences in and heritability for traits in Caucasians and for the of the were In LPA were associated with Lp(a) and ISLs in Caucasians and African of were between two ethnicities. heritability to for Lp(a) level in and family studies have Lp(a) as one of the most heritable quantitative human traits (4Kraft H.G. Kochl S. Menzel H.J. Sandholzer C. Utermann G. The apolipoprotein (a) gene: a transcribed hypervariable locus controlling plasma lipoprotein (a) concentration.Hum. Genet. 1992; 90: 220-230Crossref PubMed Scopus (229) Google Scholar, 5Austin M.A. Sandholzer C. Selby J.V. Newman B. Krauss R.M. Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes.Am. J. Hum. Genet. 1992; 51: 829-840PubMed Google Scholar, 6Hong Y. Dahlen G.H. Pedersen N. Heller D.A. McClearn G.E. de Faire U. Potential environmental effects on adult lipoprotein(a) levels: results from Swedish twins.Atherosclerosis. 1995; 117: 295-304Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 7Abney M. McPeek M.S. Ober C. Broad and narrow heritabilities of quantitative traits in a founder population.Am. J. Hum. Genet. 2001; 68: 1302-1307Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 8Mooser V. Scheer D. Marcovina S.M. Wang J. Guerra R. Cohen J. Hobbs H.H. The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans.Am. J. Hum. Genet. 1997; 61: 402-417Abstract Full Text PDF PubMed Scopus (86) Google Scholar). In with families in a high heritability estimate for the Lp(a) is the heritability of heritability were uniformly lower in African-Americans versus with family and studies have a lower heritability for Lp(a) level in Africans in and in versus Caucasians and the LPA locus almost of the genetic in Lp(a) level in Caucasians, for of the in Africans M. Kraft H.G. Lingenhel A. Delport R. Vorster E.H. Bickeboller H. Utermann G. Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians.Eur. J. Hum. Genet. 1999; 7: 169-178Crossref PubMed Scopus (55) Google Scholar). in African-American families estimated that of variation in Lp(a) level was to the LPA locus to V. Scheer D. Marcovina S.M. Wang J. Guerra R. Cohen J. Hobbs H.H. The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans.Am. J. Hum. Genet. 1997; 61: 402-417Abstract Full Text PDF PubMed Scopus (86) Google Scholar). Kraft H.G. W. Utermann G. of the in an African from the J. Hum. Genet. PubMed Scopus Google a heritability estimate for Lp(a) in an African i.e., families from In the of the type 2 repeats as the from both on the of Lp(a) level was estimated to Kraft H.G. W. Utermann G. of the in an African from the J. Hum. Genet. PubMed Scopus Google Scholar). In demonstrated the of ISLs in risk J. Paultre F. Tuck C.H. Holleran S. Reed R.G. Pearson T.A. Thomas C.M. Ramakrishnan R. Berglund L. Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.J. Lipid Full Text Full Text PDF PubMed Google Scholar, F. Pearson T.A. Tuck C.H. M. J. Reed R.G. levels of Lp(a) with a apo(a) isoform associated with coronary artery disease in African and Thromb. Vasc. Biol. PubMed Scopus Google Scholar, E. G. J. Pearson T.A. Berglund L. genotype allele-specific levels for in African the Lipid Full Text Full Text PDF PubMed Scopus Google Scholar, E. J. A. Pearson T.A. Berglund L. levels of associated with allele-specific apolipoprotein(a) levels in Clin. PubMed Scopus Google Scholar, B. Anuurad E. Zhang W. Pearson T.A. Berglund L. of and with allele-specific lipoprotein(a) levels in African Americans and Full Text Full Text PDF PubMed Scopus Google Scholar, B. Anuurad E. Zhang W. Li R. J. D. R. B. Cohen M. and allele-specific apolipoprotein(a) levels in women in the HIV Thromb. Vasc. Biol. PubMed Scopus Google Scholar). have a in lipoprotein(a) concentration associated with different apolipoprotein(a) Clin. Invest. PubMed Scopus Google Scholar, V. S. A. Guerra R. Boerwinkle E. H.J. Hobbs H.H. in the apo(a) gene associated with levels of Lp(a) in Genet. 1995; PubMed Scopus Google Scholar, F. E. E. R. P. G. U. concentrations and apolipoprotein(a) in and PubMed Google heritability from type of is The by Kraft H.G. W. Utermann G. of the in an African from the J. Hum. Genet. PubMed Scopus Google one of the to levels to estimate heritability and the effects of LPA locus on Lp(a) The estimated heritability from the of Lp(a) level for alleles by descent in and The heritability from of Lp(a) for alleles were to by a mid-parent-offspring differences between and that of Kraft H.G. W. Utermann G. of the in an African from the J. Hum. Genet. PubMed Scopus Google Scholar). African-American families a family with both parents and two Kraft H.G. W. Utermann G. of the in an African from the J. Hum. Genet. PubMed Scopus Google studied African families with a and both African-Americans and Caucasians, by for the isoform-specific Lp(a) level, estimated heritability for the larger smaller apo(a) size of a given an individual of by allele on the of the of on in families. The heritability estimate for for smaller apo(a) in African-American families was in the as in the African families. In the heritability of for larger apo(a) was generally lower in both African-Americans and Caucasians to heritable differences for larger versus smaller apo(a) isoform-specific Lp(a) In both human and of LPA alleles with two different the one with smaller apo(a) size the Lp(a) for the of B. Anuurad E. Berglund L. by and environmental and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). in that Lp(a) levels associated with apo(a) in to a higher of apo(a) isoforms for lipoprotein(a) and the of apolipoprotein(a) size on plasma lipoprotein(a) level in the Biol. Full Text PDF PubMed Google Scholar). is to that of larger apo(a) to environmental in a lower of heritability as in the for a of and with a genetic two different higher Lp(a) levels in for the apo(a) compared with Marcovina S.M. D. E. M. of lipoprotein(a) in African Americans and for a 1997; PubMed Scopus Google Scholar). We have that with human Lp(a) levels and of the of an environmental B. Anuurad E. Zhang W. Li R. J. D. R. B. Cohen M. of on Lp(a) level in women with HIV in the HIV Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). We further noted different heritability between younger and older families. In Caucasians, traits were heritable in both groups with a higher estimate in older versus younger families. In in a lower heritability was noted in older versus younger families for Although results with two a of heritability have heritability in versus of that the amount of variation in genetic effects on Lp(a) to variation in environmental by and to in variation to and that a of genetic environmental different of in ethnic that in larger studies and that the of the of to families to further the in heritability across the In the of apo(a) were between African-Americans and the to 4-fold higher Lp(a) and ISLs in African-Americans versus Caucasians to differences in LPA We association on genetic for both ethnic groups in a and differences in of of association and level of by ethnic the effects were for of In a by C. D. A. E. N. in LPA most of the variation in Lp(a) levels in African PubMed Scopus Google the the association and of Lp(a) level In with was associated with Lp(a) level as as Lp(a) level carried by the smaller apo(a) in In of and in African-Americans and Caucasians, for were to noted by C. D. A. E. N. in LPA most of the variation in Lp(a) levels in African PubMed Scopus Google Scholar). two of LPA with Lp(a) levels in the two ethnic the of a in the genetic for Lp(a) across human the size of were associated for and in with families an overall to the for and with of apo(a) and to larger and smaller apo(a) sizes. to have in genetic In on the of the number of type 2 repeats an We that Lp(a) to associated with larger LPA to of a single type family a the of a of on genetic as was carried for a single gene than In of not of in apo(a) genetic between parents and for given to unique is to LPA linked to a allele in association with larger smaller allele size of a given of on the two LPA and of to on in the In conclusion, traits associated with the smaller LPA allele were strongly determined by genetics, although with a varying of ethnic influence. The that the alleles effects across ethnicities. studies on and differences in heritability and in the of genetic control by to of the of in populations and on the of cardiovascular risk The of the of with by descent kringle 4 isoform-specific apo(a) level lipoprotein (a)