Impact of a common mutation of the LDL receptor gene, in French-Canadian patients with familial hypercholesterolemia, on means, variances and correlations among traits of lipid metabolism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65502/1/j.1399-0004.1995.tb03925.x.pd

Large amplitude shock wave motion in two dimensional transonic channel flows

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76053/1/AIAA-1978-247-401.pd

Smoking and reverse cholesterol transport: evidence for gene-environment interaction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66077/1/j.1399-0004.1989.tb03201.x.pd

A biometrical study of the relationship between sodium-lithium countertransport and triglycerides

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66400/1/j.1469-1809.1997.6120121.x.pd

Influence of apolipoprotein E genotype variation on the means, variances, and correlations of plasma lipids and apolipoproteins in children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65894/1/j.1469-1809.1999.6340311.x.pd

Contrasting multi-site genotypic distributions among discordant quantitative phenotypes: the APOA1/C3/A4/A5 gene cluster and cardiovascular disease risk factors

Most tests of association between DNA sequence variation and quantitative phenotypes in samples of randomly chosen individuals rely on specification of genotypic strata followed by comparison of phenotypes across these strata. This strategy often succeeds when phenotypic differences are caused by one or two single nucleotide polymorphisms (SNPs) among the surveyed markers. However, when multiple-SNP haplotypes account for observed phenotypic variation, identification of the best partitioning requires examination of an inordinate number of SNP combinations. An alternative approach is to rank individuals by their phenotypic measures and ask whether attributes of the genotypic variation show a non-random distribution along this phenotypic ranking. One simple version of this strategy selects the top and bottom tails of the distribution, and then tests whether genotypes from these two samples are drawn from a single population. This framework does not require the recovery of phased haplotypes and allows contrasts between large numbers of sites at once. We use a method based on this approach to identify associations between plasma triglyceride level, a risk factor for cardiovascular disease, and multi-site genotypes located in the APOA1/C3/A4/A5 cluster of apolipoprotein genes in unrelated individuals (1,071 African-American females, 780 African-American males, 1,036 European-American females, and 930 European-American males) sampled from four US cities as part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Method performance is investigated using simulations that model genealogical variation and different genetic architectures. Results indicate that this multi-site test can identify genotype-phenotype associations with reasonable power, including those generated by some simple epistatic models. Genet. Epidemiol . 2006. © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55790/1/20163_ftp.pd

Utility of the predictors of coronary heart disease mortality in a longitudinal study of elderly Finnish men aged 65 to 84 years is dependent on context defined by Apo E genotype and area of residence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65869/1/j.1399-0004.1999.560505.x.pd

Association between common alleles of the low-density lipoprotein receptor gene region and interindividual variation in plasma lipid and apolipoprotein levels in a population-based sample from Rochester, Minnesota

This paper presents an analysis of the relationship between variation in the low-density lipoprotein receptor (LDLR) gene region and interindividual variation in plasma lipid and apolipoprotein levels in a sample representative of the adult population of Rochester, Minn. (217 females and 187 males aged 26 to 63). This relationship was analyzed by estimating the average excesses of alleles of the LDLR gene defined using RFLP markers both singly and simultaneously. We also used a cladistic approach to illustrate the consequences of incorporating evolutionary information into the analysis of genotype-phenotype relationships. Although results from both approaches supported the inference that common variation in the LDLR gene region associates with small effects on plasma lipid and apolipoprotein levels, only the cladistic approach provides direction for further work aimed at identifying the functional DNA sequence variations responsible for the observed associations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42270/1/439-99-1-108_60990108.pd

A path analysis of the causal relationships between red cell glycolytic intermediates, ADP and ATP in sickle cell anemia

The statistical relationships among the glycolytic intermediates (GIs) of the Embden-Meyerhof pathway, adenine nucleotides (ANs) and various hematological measures were estimated for 34 sickle cell anemia patients. Heterogeneity in linear and quadratic regressions of hemoglobin and hematocrit, both singly and jointly, on the GI and AN variables implied 1) that any single formula to standardize optical density measures of the GIs and ANs on a per gram hemoglobin or per liter cell water basis would not uniformly remove hemoglobin and hematocrit effects; 2) that ignoring significant hematological effects could bias the estimates of correlation among GIs and ANs; and 3) that hemoglobin and hematocrit measures do not reflect the same source of variability.The correlations among the GIs and ANs, after adjustment for hematological variability, were analyzed by path analysis to determine which of five proposed path models for cause and effect relationships were compatible with the data. AMP had a greater influence on ADP (coefficient of determination (CD) = 23%) than all the GIs together, while G6P and ADP influenced ATP variability the most (CD = 33% and 12%). The contributions of unknown factors to ADP and ATP variability were large for all models (CD = 56-77%) possibly due to stress of sickle cell disease. The path model with AMP and the four GIs (G6P, F6P, FDP, DHAP) influencing ADP variation, and the same GIs and ADP influencing ATP was the model most compatible with the data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22789/1/0000345.pd

Heterogeneity of the blood pressure distribution among Solomon Islands societies with increasing acculturation

This study illustrates the very complex nature of gene by environmental interactions influencing the blood pressure (BP) distribution in a series of genetically distinctive populations undergoing rapid acculturation. We report the results of two BP and anthropometric surveys on Solomon Islands societies separated by an interval of 14 to 19 years. While differences in acculturation existed at the time of the initial survey, the interval between surveys was marked by rapid acculturation in almost all societies. Seven of the eight societies originally covered were included in the resurvey, and a large but variable proportion of the original sample subjects was recovered in the follow-up. Because the genetic relationships of the societies have been described, we were able to establish the following points concerning the role of genetic differences in determining the distribution of BP among these populations and, more important, the interaction of these genetic differences with changes associated with increasing acculturation: 1) In the initial survey, mean adjusted systolic and diastolic BPs were significantly heterogeneous among societies within and among genetically related clusters of societies (genetic clusters) and sexes. At the same time, rank differences in these means were not associated with rank differences in acculturation status among societies ignoring cluster membership. 2) Importantly, in the follow-up survey increasing acculturation resulted in the disappearance of significant differences in mean systolic and diastolic BP among genetic clusters in males , despite continued significant heterogeneity among societies within genetic clusters. In females, differences among genetic clusters persisted, but the degree of significance was substantially less with increasing acculturation. We interpret these changes as evidence for genotype by environment interaction. 3) There were significant differences in interindividual variances of both systolic and diastolic BPs among genetic clusters in the first survey. Ranks of these variances were not significantly associated with acculturation rank. In the follow-up survey, however, most societies showed striking increases in the variance of both systolic and diastolic BPs with increased acculturation. These increases in variance of both systolic and diastolic BPs may be related to a) shifts in demography and/or anthropometry of some societies; b) increased range and intensity of environmental factors affecting BP and associated with increased acculturation; and/or c) genotype by environmental interactions. 4) The correlation between systolic and diastolic BP decreased over the interval for all societies within and among genetic clusters. This trend was partly the result of larger changes in variances for systolic than diastolic BP in the resurveys. This study illustrates the enormous heterogeneity in the BP distribution that can occur even among populations with relatively similar ethnic and cultural backgrounds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37648/1/1330810406_ftp.pd