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Weighted genetic risk score (wGRS) was analysed for association with disease activity in more than 500 MS patients before and during interferon-beta treatment. The wGRS was higher in MS patients than in healthy controls when analysing eight HLA - and 109 non-HLA MS risk gene variants. No significant associations were observed between number of relapses prior to or during treatment with interferon-beta, both with and without HLA risk alleles included in the wGRS. In conclusion, among Danes the wGRS was higher in MS patients than controls but was not associated with the overall disease activity or response to treatment with interferon-beta. [ABSTRACT FROM AUTHOR]

Abstract: We discuss categories of genetic diversity in humans. Neutral diversity, population differences in frequencies of genetic markers that we think are invisible to natural selection, provides a passive record of population history but is otherwise of little interest in human biology. Genetic variation related to disease can be separated into mutational noise and variation due to selection, either ongoing selection else effects of a past environment. We distinguish consequences of genetic diversity for fitness, relevant to evolution, and consequences for well-being, relevant to medicine and public health. We call genetic variation that causes impairment of health or well-being of individual humans “apparent genetic burden” and variation that has effects on fitness but not well-being “unapparent genetic burden”. We use “burden” to distinguish these notions from the classical concept of “genetic load” that refers to effects on population fitness, a concept formulated by Morton et al. [Morton, N.E., Crow, J.F., Muller, H.J., 1956. An estimate of the mutational damage in man from data on consanguineous marriages. Proc. Natl. Acad. Sci. U.S.A. 42, 855–863]. We distinguish adapted genes and adapted genotypes: an adapted gene is a gene that increases fitness of its bearer either in heterozygous or homozygous state or both, while an adapted genotype is a genotype that increases fitness of its bearer but is not transmitted intact to future generations. Balanced polymorphisms in which the heterozygote is superior in fitness may generate most adapted genotypes. In the face of major rapid environmental change adapted genotypes appear first but over time they are replaced by adapted genes. The presence of adapted genotypes is a good indication of recent environmental change: for example, there are apparently many polymorphisms in domestic animals of this nature, responses to domestication, and many fewer in wild animals (and in humans). [Copyright &y& Elsevier]

Background: Single polymorphisms of different genes have been associated with coronary artery disease (CAD). The aim of this study was to evaluate the benefit of analyzing multiple genetic polymorphisms as a compound unit to assess the individual genetic burden for CAD. Methods and Results: The study population consisted of 100 case patients with, and 100 control patients without, angiographically proven CAD. The patients were matched for age, sex, and numbers of standard cardiac risk factors. Sixteen different genetic polymorphisms were analyzed using polymerase chain reaction-based technologies. None of these polymorphisms showed a significant difference in the allele frequency between case and control patients. Eight genes with a higher allele frequency in the case group (delta allele frequency >0.05) were defined as risk alleles (RA) and subsequently tested as a compound unit. A risk stratification for 64.5% of all patients was possible when eight genes with their 16 RA were included in the analysis. With more than eight RA per individual, the odds ratio for developing CAD was 3.21 (95% CI 1.77–5.82, P<0.001). However, there was still an overlap in the number of RA in case and control patients. A computer simulation estimated that more than 200 polymorphisms were needed for a reasonable genetic discrimination for patients at risk for CAD. Conclusions: An increasing number of risk alleles are associated with an elevated risk for CAD. An analysis of multiple polymorphisms, some several hundred, each with a small impact, may allow improved assessment of the individual genetic burden for CAD. Larger studies are needed to prove this hypothesis. [Copyright &y& Elsevier]