Divergence of values and goals in participatory research

Public participation in scientific research has gained prominence in many scientific fields, but the theory of participatory research is still limited. In this paper, we suggest that the divergence of values and goals between academic researchers and public participants in research is key to analyzing the different forms this research takes. We examine two existing characterizations of participatory research: one in terms of public participants' role in the research, the other in terms of the virtues of the research. In our view, each of these captures an important feature of participatory research but is, on its own, limited in what features it takes into account. We introduce an expanded conception of norms of collaboration that extends to both academic researchers and public participants. We suggest that satisfying these norms requires consideration of the two groups' possibly divergent values and goals, and that a broad characterization of participatory research that starts from participants' values and goals can motivate both public participants’ role in the research and the virtues of the research. The resulting framework clarifies the similarities and differences among participatory projects and can help guide the responsible design of such projects.     

The feasibility of making short-term migration estimates

Short-term migration, that is stays of less than 12 months, has received particular attention recently from both national and local level users of population statistics. This interest is part of the wider interest shown in increasing levels of long-term migration statistics in recent years. This article is an initial assessment by ONS of the potential to produce short-term migration estimates for England and Wales, and the challenges faced in doing so. Central to these challenges is the question of how short-term migration should be defined. In addition, illustrative estimates of short-term migration based on the International Passenger Survey (IPS) are provided. These illustrative estimates, along with associated standard errors, are provided at both national and regional levels using a number of definitional bases.     

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Out of Africa again and again

The publication of a haplotype tree of human mitochondrial DNA variation in 1987 provoked a controversy about the details of recent human evolution that continues to this day. Now many haplotype trees are available, and new analytical techniques exist for testing hypotheses about recent evolutionary history using haplotype trees. Here I present formal statistical analysis of human haplotype trees for mitochondrial DNA, Y-chromosomal DNA, two X-linked regions and six autosomal regions. A coherent picture of recent human evolution emerges with two major themes. First is the dominant role that Africa has played in shaping the modern human gene pool through at least two--not one--major expansions after the original range extension of Homo erectus out of Africa. Second is the ubiquity of genetic interchange between human populations, both in terms of recurrent gene flow constrained by geographical distance and of major population expansion events resulting in interbreeding, not replacement.