A systematic review of the association between circulating concentrations of C reactive protein and cancer.

The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case-control or cross-sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene-cancer association studies would be valuable in investigating the role of CRP in cancer

Erratum to: Causal inference-so much more than statistics.

In the print version and online PDF of this article, in Scenario 2 in the extended caption to Figure 1 (page 1898), the first path should read PE-Smoking-Addictive personality-Obesity rather than PE-SEP-Smoking-Addictive personality-Obesity and in the following sentence or SEP should not have been included. In the online version of this paper, the extended caption was omitted from Figure 1 in both the downloadable Powerpoint slide and the html version that opens in a new tab. The html version also omitted the image and incorrectly included a section of text from the paper that did not pertain to Figure 1. Further, the image was also omitted from the html version of Figure 2 that opens in a new tab, and that html version also incorrectly included a section of text from the paper that did not pertain to Figure 2. The article has been corrected

Association between falls in elderly women and chronic diseases and drug use: cross sectional study.

OBJECTIVE: To assess the associations between having had a fall and chronic diseases and drug use in elderly women. DESIGN: Cross sectional survey, using data from the British women's heart and health study. SETTING: General practices in 23 towns in Great Britain. PARTICIPANTS: 4050 women aged 60-79 years. MAIN OUTCOME MEASURE: Whether women had had falls in the previous 12 months. RESULTS: The prevalence of falling increased with increasing numbers of simultaneously occurring chronic diseases. However, no such relation with falling was found in the fully adjusted data for the number of drugs used. Circulatory disease, chronic obstructive pulmonary disease, depression, and arthritis were all associated with an increased odds of falling. The fully adjusted, population attributable risk of falling associated with having at least one chronic disease was 32.2% (95% confidence interval 19.6% to 42.8%). Only two classes of drugs (hypnotics and anxiolytics, and antidepressants) were independently associated with an increased odds of falling. Each class was associated with an increase of about 50% in the odds of falling, and each had a population attributable risk of < 5%. CONCLUSION: Chronic diseases and multiple pathology are more important predictors of falling than polypharmacy

Obstetrician-assessed maternal health at pregnancy predicts offspring future health

Background: We aimed to examine the association between obstetrician assessment of maternal physical health at the time of pregnancy and offspring cardiovascular disease risk.&lt;p&gt;&lt;/p&gt; Methods and Principal Findings: We examined this association in a birth cohort of 11,106 individuals, with 245,000 person years of follow-up. We were concerned that any associations might be explained by residual confounding, particularly by family socioeconomic position. In order to explore this we used multivariable regression models in which we adjusted for a range of indicators of socioeconomic position and we explored the specificity of the association. Specificity of association was explored by examining associations with other health related outcomes. Maternal physical health was associated with cardiovascular disease: adjusted (socioeconomic position, complications of pregnancy, birthweight and childhood growth at mean age 5) hazard ratio comparing those described as having poor or very poor health at the time of pregnancy to those with good or very good health was 1.55 (95%CI: 1.05, 2.28) for coronary heart disease, 1.91 (95%CI: 0.99, 3.67) for stroke and 1.57 (95%CI: 1.13, 2.18) for either coronary heart disease or stroke. However, this association was not specific. There were strong associations for other outcomes that are known to be related to socioeconomic position (3.61 (95%CI: 1.04, 12.55) for lung cancer and 1.28 (95%CI:1.03, 1.58) for unintentional injury), but not for breast cancer (1.10 (95%CI:0.48, 2.53)).&lt;p&gt;&lt;/p&gt; Conclusions and Significance: These findings demonstrate that a simple assessment of physical health (based on the appearance of eyes, skin, hair and teeth) of mothers at the time of pregnancy is a strong indicator of the future health risk of their offspring for common conditions that are associated with poor socioeconomic position and unhealthy behaviours. They do not support a specific biological link between maternal health across her life course and future risk of cardiovascular disease in her offspring.&lt;p&gt;&lt;/p&gt

Genetic Markers as Instrumental Variables

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from epidemiologists, economists, statisticians and social scientists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. Although these have been discussed in the epidemiological, medical and statistical literature, they have not been well-defined in the economics and social science literature. The increasing availability of biomedical data however, makes understanding of these conditions crucial to the successful use of genotypes as instruments for modifiable risk factors. We combine the econometric IV literature with that from genetic epidemiology using a potential outcomes framework and review the IV conditions in the context of a social science application, examining the effect of child fat mass on academic performance.ALSPAC; Fat mass; Genetic Variants; Instrumental Variables; Mendelian Randomization; Potential Outcomes

Genetic Markers as Instrumental Variables:An Application to Child Fat Mass and Academic Achievement

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. We combine the IV literature with that from genetic epidemiology, with an application to child adiposity (fat mass, determined by a dual-energy X-ray absorptiometry (DXA) scan) and academic performance. OLS results indicate that leaner children perform slightly better in school tests compared to their more adipose counterparts, but the IV findings show no evidence that fat mass affects academic outcomes.Instrumental variables; Mendelian randomization; Genetic variant; Potential outcomes; Academic performance; Educational attainment; Adiposity; Fat mass; Body Mass Index; ALSPAC

Genome-wide association study identifies common and low-frequency variants at the AMHgene locus that strongly predict serum AMH levels in males

Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 M ‘1000 Genomes Reference Panel’ imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (PMale = 2 × 10−49, Beta: ∼0.9 SDs per allele), rs8112524 (PMale = 3 × 10−8, Beta: ∼0.25)] and low-frequency variants [rs2385821 (PMale = 6 × 10−31, Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (PHet 0.0003–6.3 × 10−12), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men

Child height, health and human capital: evidence using genetic markers

Height has long been recognised as associated with better outcomes: the question is whether this association is causal. We use children’s genetic variants as instrumental variables (IV) to deal with possible unobserved confounders and examine the effect of child and adolescent height on a wide range of outcomes: academic performance, IQ, self-esteem, symptoms related to depression and behavioural problems, including hyperactivity, emotional, conduct and peer problems. OLS findings show that taller children have higher IQ scores, perform better in school tests, and are less likely to have emotional or peer problems. The IV results differ. They show that taller children have better cognitive performance but, in contrast to the OLS, indicate that taller children are more likely to have behavioural problems. The magnitude of these IV estimates is large. For example, the effect of one standard deviation increase in height on IQ is comparable to the IQ difference for children born approximately 6 months apart within the same school year, while the increase in hyperactivity is comparable to the raw difference in hyperactivity between boys and girls.Child and adolescent height; human capital; mental health; behavioural outcomes; instrumental variables; Mendelian randomization; genetic variants; ALSPAC