confidentiality in relation to genomic data [19]. The rise in the sheer number of available data sources, in both the com- mercial and public sectors [20], coupled with the ease with which an individual’s DNA can be (and is) analysed, suggests that the context for data release has changed. Disregarding this takes for grant- ed the support of participants and the wider public for genomic research in a way that could have damaging conse- quences for future scientific endeavours. Martin Bobrow’s Viewpoint: Toward a Middle Ground Genuinely new ethical questions are rare, but difficult forms of old questions are exercising genomics researchers. Al- though posed as questions arising from GWAS or large cohort studies, the issues actually derive mainly from funders’ pressure to encourage wide sharing of basic research data and from the power of the Internet as a tool for data sharing. If researchers simply kept their data to themselves, there would be no problem. Making data available to many intelli- gent minds maximises the likelihood that the benefits of research will rapidly be returned to society, but also maximizes opportunity for breaching the duty of privacy to research participants. One way people attempted to reconcile these objectives was to make only aggregated genotype data publicly accessible on the Internet, with restricted access to data giving individual participants’ genotypes. The landmark paper of Homer et al. shows, as is in retrospect intuitively obvious, that this doesn’t work. The presence of an individual’s DNA can be detected even if it is a very minor component of a mixture, and it is therefore possible that, under very special circum- stances, an outsider could deduce that a named individual was part of, for example, a group of patients with a specific disease—the anonymised data could be re-identified. To react to this surprising turn of events by abandoning large-scale genomic stud- ies, or reducing the pressure for data sharing, would, in my view, be a dispro- portionate response to the level of threat as we currently see it. A widely discussed option is to get very explicit consent from patients. I would take it for granted that researchers must be open and honest with volunteer participants, but long, detailed technical consent documents tend to obfuscate, rather than illuminate, and may be better at shifting the legal burden than actually informing research partici- pants. As such, they do little to engender the essential ‘‘trusting relationship’’ that should exist between the research com- munity, research participants, and the public. How, then, should we react to this new state of affairs? 1. Major research databases have already moved aggregated genomic data from open Internet access to restricted sites where researchers can gain access in return for undertakings on appropriate data use. Provided these mechanisms do not become overly onerous and that they can be given sufficient teeth to ensure that the obligations are en- forced, this will not be a major obstacle to utilization of the data and could be retained indefinitely. 2. I wish it were clearer as to whether deliberately misusing data to re-estab- lish the identity of anonymised individ- uals is a legally punishable offense. It breaches fundamental principles of data protection, but clear statements of penalties and the intention to enforce these would be extremely helpful. The law in any one country would not, of course, stop a malign individual in a distant jurisdiction, but it would seriously inhibit the use of his or her efforts by state agencies, police, insurers, and others in the data sub- ject’s own country, and without that there is little risk of harm. 3. The risk of harm to a research participant often comes not so much from their participation in the research, but from other activities, such as hospital data keeping, private sector genome studies, etc., which allow some genomic data associated with identify- ing characteristics of the individual to become accessible to the malign data miner. Without that, the ‘‘Homer’’ phenomenon has limited power to harm. Widespread public discussion to alert people and regulatory agencies to the dangers of having named genomic data lying in potentially accessible places is needed. 4. We all have confidential relationships with many people—lawyers, bankers, doctors—whom we trust because they are bound by professional codes of conduct with enforceable penalties. Research scientists, and particularly the institutions that employ them, probably need to make their own position in this regard more explicit— there should be clear codes of conduct and penalties for breaching them. Further knee-jerk reactions should be avoided. More research will clarify exactly how sensitive these methods for re-identi- fying individuals are, particularly in rela- tion to the choice of appropriate reference populations. I would hope the next 12 months would produce greater clarity and time to develop a proportionate long-term response. Bruce Weir’s Viewpoint: Individual Genotyping in Forensics and GWAS Contexts Braun et al. [2] and Visscher and Hill [3] have given helpful analyses of the question discussed by Homer et al. [1]: does an individual with a known genotype belong to a sample of individuals for which only allele frequencies are known? The analyses of all these authors suppose that allele frequencies are known also for a reference sample, and the question could be rephrased as: is this proband a member of this test sample of individuals, or of this reference sample, or neither sample? Homer et al. phrased their discussion in a forensic context where there is often interest in knowing whether or not a particular person was a contributor to a mixed sample of DNA from more than one person. They made brief mention of GWAS for which allele frequencies, but not individual genotypes, are made pub- licly available and where there may be interest in knowing whether or not a particular person was a member of a study. The resulting attention to this second situation, and the restriction of access to GWAS allele frequencies by the NIH and the Wellcome Trust, is likely the reason why Braun et al., as well as Visscher and Hill, concentrated on this situation and made only brief mention of forensic applications. Braun et al. employed both simulated and real data to show that the original analysis of Homer et al. is susceptible to linkage dis- equilibrium among the markers, the dif- ferences in allele frequencies between test and reference samples, and the relative sizes of these two samples. They also looked at the effects of the proband having a relative in either sample. Their work showed high specificity for the test statistic of Homer et al., but with the possibility of low sensitivity. Although forensic science is not their main focus, Visscher and Hill introduce their treatment with likelihood ratios, as do forensic scientists in assessing how data support competing hypotheses. In this case, the two hypotheses are that the proband is either a member of the test PLoS Genetics | www.plosgenetics.org 3 October 2009 | Volume 5 | Issue 10 | e1000665