Do Participants in Genome Sequencing Studies of Psychiatric Disorders Wish to Be Informed of Their Results? A Survey Study

<div><p>Objective</p><p>As large-scale genome sequencing technology advances, concerns surrounding the reporting of individual findings to study volunteers have grown and fueled controversy. This is especially true in mental health research, where the clinical importance of sequencing results is particularly unclear. The ethical, legal, and social issues are being widely debated, but less is known about the attitudes of actual study volunteers toward sequencing studies or what they wish to learn about their DNA sequence and its health implications. This study provides information on psychiatric research volunteers’ attitudes, beliefs, and concerns with respect to participation in DNA sequencing studies and reporting of individual results.</p><p>Method</p><p>We conducted a pilot study using a questionnaire that we developed to assess what information volunteers in an ongoing family study of bipolar disorder would like to receive if they underwent genome sequencing, what they would do with that information, and what concerns they may have.</p><p>Results</p><p>Almost all of the respondents were willing to participate in genome sequencing. Most respondents wished to be informed about all their health-related genetic risks, including risks for diseases without known prevention or treatment. However, few respondents felt well informed about the nature of genome sequencing or its implications for their health, insurability, or offspring.</p><p>Conclusions</p><p>Despite generally positive attitudes toward genome sequencing among study volunteers, most are not fully aware of the special issues raised by genome sequencing. The attitudes of study volunteers should be considered in the debate about the reporting of individual findings from genome sequencing.</p></div

Participant characteristics.

1<p>Denominator is 58 within each category.</p>2<p>Rounded to nearest whole percent.</p

What would be the most important things to know?

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101111#pone-0101111-g001" target="_blank">Figure 1</a> illustrates participants’ responses to the survey question, “What would be the most important [health information] to know?” in a word cloud, with size directly related to the commonality of the word used in the responses. The word cloud was created using online software at <a href="http://www.tagxedo.com" target="_blank">www.tagxedo.com</a>. We entered the text from the participants’ responses free responses. For clarity, we removed common everyday words, combined related words, and set the emphasis to 80%, the maximum word count to 50, tightness to 100%, color variation to 50%, and spread frequency to 20. We edited the style and format for legibility.</p

Highlighted survey responses.

1<p>Denominator may not equal 58 due to missing responses or multiple answers possible.</p>2<p>Rounded to nearest whole percent.</p

Heritability (diagonal) and Genetic Correlations (above diagonal)^a.

a<p>Mean and standard deviation.</p><p>**P≤0.01,</p><p>*P≤0.05.</p

Significance levels of covariates and corresponding beta coefficients, by sub-regions of the corpus callosum.

ns<p>P>0.05.</p

Demographic data.

<p>Demographic data.</p

T1-weighted mid-sagittal view of the corpus callosum (CC).

<p>Six sub regions are shown: CC1 (genu), CC2, CC3, CC4, CC5 and CC6 (splenium).</p

Genome-wide association results and detailed peak association regions.

<p>(<b>A</b>) Manhattan plot of the meta-analysis performed on early-onset bipolar patients and controls from France and Germany. Physical position is shown along the <i>x</i> axis and –log10(<i>P</i>-value) is shown along the <i>y</i> axis. (<b>B</b>) Detail of the two most associated regions on chromosomes 5p13 and 12p12. Allele frequency differences are represented by –log10(<i>P</i>-values) for the French (open grey circles), the German (open grey squares) and the meta- (open red diamonds) analyses. Grey crosses represent –log10(<i>P</i>-value) for imputed ungenotyped SNPs. The most associated SNP for each region is shown with orange circle. On chromosome 12p12, the lowest <i>P</i>-value (<i>P</i> = 2.1×10⁻⁷) was observed for an imputed SNP (<i>rs10743315</i>). On chromosome 5p13, the lowest <i>P</i>-value (<i>P</i> = 2.6×10⁻⁷) was observed for a three-SNPs window haplotype (light blue line) located downstream to <i>OXCT1</i> and upstream to <i>PLCXD3</i> (<i>rs624097-rs316762-rs10512793</i>). The genome-wide significant threshold (<i>P</i> = 5×10⁻⁸) is indicated by the blue dash line and the dot black line shows a threshold at <i>P</i> = 5×10⁻⁵. The largest differences in allele frequencies are represented with filled diamonds. Gene position and annotation (<a href="http://genome.ucsc.edu/" target="_blank">http://genome.ucsc.edu/</a>) are symbolised by green arrows. Linkage disequilibrium (r²) estimated according to HapMap CEU population SNPs (release 3) is symbolised in the bottom part of each figure. Darker red indicates higher values.</p

Regions associated at <i>P</i><5×10⁻⁵ with early-onset BD in meta-analysis.

<p>OR, odds ratio; Q, <i>P</i>-value for Cochrane's Q statistic; I², heterogeneity index.</p>a<p>position from the short arm telomere based on Hg18.</p