The use of race, ethnicity and ancestry in human genetic research

Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008–2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001–2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using ‘race’, ‘ethnicity’ or ‘ancestry’ defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using ‘ancestry’ being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated

Does the method of lung preservation influence outcome after transplantation?

ObjectiveDespite 50 years of lung preservation research, the optimal preservation technique is undefined. Using data from a national cohort, we investigated outcomes with different preservation methods after adult lung transplantation.MethodsEarly (30-day), late (30-day to 3-year), and overall (3-year) mortalities, adjusted for differences in donor and recipient characteristics, were compared by using Cox regression. Intensive care unit length of stay and the number of rejection episodes were secondary outcomes.ResultsSix hundred eighty-one eligible lung transplantations between July 1995 and June 2003 were preserved with Euro–Collins solution (n = 284), blood albumin (n = 139), core cooling (n = 107), or low potassium dextran solution (n = 151). There was significantly increased use of low potassium dextran solution over time (P < .001). Unadjusted 3-year survival was similar across the groups (P = .72), with the highest 3-year survival in the low potassium dextran group (62%; 95% confidence interval, 51%–72%) and the lowest in the blood albumin group (49%; 95% confidence interval, 39%–58%). Risk-adjusted early (P = .70), late (P = .27), and overall (P = .72) survival was similar across the groups and was not affected by ischemic time. Freedom from death caused by primary graft dysfunction was again highest in the low potassium dextran group (95%; 95% confidence interval, 90%–98%) and lowest in the blood albumin group (91%; 95% confidence interval, 85%–95%). There was no difference in intensive care unit length of stay. An increased incidence of rejection was apparent with increasing ischemic time (P = .067).ConclusionThe methods of lung preservation in current use do not seem to affect early or midterm survival after transplantation, but increasing ischemic time might predispose to increased rejection