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Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases. 相似文献
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Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction. 相似文献
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By injecting small amounts of CO2 through a needle, one can move bowel or bladder from the intended path of instruments during interventional procedures. The technique worked well in six of seven cases in the pelvis and retroperitoneum; it was not effective in the mediastinum or midabdomen (n = 6). 相似文献
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Approximately one quarter of a series of 45 schizophrenic and schizoaffective patients with operationally diagnosed episodes of postpsychotic depression were also found to have anxiety symptoms consistent with the panic-attack syndrome. The incidence of such attacks was distributed across all demographic groups. Heuristic and treatment implications of this observation are considered. 相似文献
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Stefanie Sarantopoulos Kristen E Stevenson Haesook T Kim Nazmim S Bhuiya Corey S Cutler Robert J Soiffer Joseph H Antin Jerome Ritz 《Clinical cancer research》2007,13(20):6107-6114
PURPOSE: Recent studies suggest that donor B cells as well as T cells contribute to immune pathology in patients with chronic graft-versus-host disease (GVHD). B-cell activating factor (BAFF) promotes survival and differentiation of activated B cells. Thus, we tested whether BAFF correlated with chronic GVHD disease activity and time of onset after allogeneic hematopoietic stem cell transplantation (HSCT). EXPERIMENTAL DESIGN: Patients who had undergone allogeneic HSCT between 1994 and 2005 for hematologic malignancies were studied. ELISA was used to measure plasma BAFF levels and flow cytometry was used to assess BAFF receptor expression on B cells in patients with or without chronic GVHD. RESULTS: In 104 patients, BAFF levels were significantly higher in patients with active chronic GVHD compared with those without disease (P = 0.02 and 0.0004, respectively). Treatment with high-dose prednisone (>or=30 mg/d) was associated with reduced BAFF levels in patients with active chronic GVHD (P = 0.0005). Serial studies in 24 patients showed that BAFF levels were high in the first 3 months after HSCT but subsequently decreased in 13 patients who never developed chronic GVHD. In contrast, BAFF levels remained elevated in 11 patients who developed chronic GVHD. Six-month BAFF levels >or=10 ng/mL were strongly associated with subsequent development of chronic GVHD (P < 0.0001). Following transplant, plasma BAFF levels correlated inversely with BAFF receptor expression on B cells (P = 0.01), suggesting that soluble BAFF affected B cells through this receptor. CONCLUSION: These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD. 相似文献
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外科医生和手术室人员经常接触手术设备产生的烟气,病人也会暴露于烟气中,特别是腹腔镜手术中产生的烟气滞留于腹腔内这一密闭空间并被吸收.这些烟气是一种与香烟烟气相似的毒性物质,然而对这种毒性物质的影响还未引起足够重视.应该采取必要措施尽可能减少手术中烟气的不良影响. 相似文献
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