warfarin and Multiple-Sclerosis

With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.. We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.. This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.

Topics: Anticoagulants; Asian People; Chromosome Mapping; Diabetes Mellitus; DNA Copy Number Variations; Female; Genetic Predisposition to Disease; Genetic Variation; Genome, Human; Genome, Mitochondrial; Haplotypes; Hemorrhage; Humans; Hypoglycemic Agents; India; Metformin; Middle Aged; Multiple Sclerosis; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Warfarin

When undertaking indirect comparisons, relative risk (RR) is often suggested as an appropriate indicator of treatment effect, particularly where baseline (common comparator) risks differ. In this article, we demonstrate that such use of RR in indirect comparisons is not necessarily stable with respect to framing of outcomes.. Use of RR is shown to lead to inferential fallacies where, for example, a new therapy is suggested to reduce both mortality and survival risk. Conditions under which the inferential fallacy arises and an odds solution are illustrated in indirect comparison of natalizumab and interferon beta-1b for multiple sclerosis.. Using RR, natiluzimab is suggested to be 30% more effective than interferon for progression (RR=0.70), but 16% less effective than interferon for no progression (RR=0.84). This inferential anomaly is avoided using odds ratios (ORs), with odds of progression (0.83) the reciprocal of that for no progression (1.21).. Inferential fallacies with use of RR in indirect comparison provide scope for abuse with respect to choice in framing of outcomes, and confound decision making where both results are presented. The use of ORs overcomes this inferential fallacy, consistently informing inference with respect to direction of treatment effect in indirect comparisons.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Aspirin; Atrial Fibrillation; Humans; Interferon beta-1b; Interferon-beta; Multiple Sclerosis; Natalizumab; Odds Ratio; Randomized Controlled Trials as Topic; Research Design; Risk; Stroke; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Warfarin

Two patients who were taking warfarin experienced significant prolongations of the prothrombin time (protime) after treatment with high-dose corticosteroids for rapid progression of MS. This complication of therapy is potentially life-threatening.

Topics: Adrenal Cortex Hormones; Adult; Anticoagulants; Aortic Valve Stenosis; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Valve Prosthesis; Heparin; Humans; Middle Aged; Multiple Sclerosis; Prothrombin Time; Warfarin