Supplementary Material for: <i>LPA</i> and <i>PLG</i> Sequence Variation and Kringle IV-2 Copy Number in Two Populations

<i>Background/Aims:</i> Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic <i>LPA</i> kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations. <i>Methods:</i> To identify potential cis-acting factors, we re-sequenced the gene <i>LPA</i> for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen <i>(PLG)</i> and genotyped the kringle IV copy number variant in the same reference samples. <i>Results:</i> These data are the most comprehensive description of sequence variation in <i>LPA</i> and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of <i>LPA</i> sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within <i>PLG </i>are not in linkage disequilibrium with SNPs in <i>LPA</i>, and we show that kringle IV copy number variation is not in linkage disequilibrium with either <i>LPA</i> or <i>PLG</i> SNPs. <i>Conclusions:</i> Together, these data suggest that <i>LPA</i> SNPs could independently contribute to Lp(a) levels in the general population.