Archive for the 'Friday Links' Category

In this week’s Nature Genetics there is a genome-wide association study of lung disease severity in cystic fibrosis suffers (or at least the subset who carry the ΔF508 mutation). The authors report a number of variants with “suggestive evidence”, and one with genome-wide significant evidence . The one genome-wide significant variant is rs12793173, with the C allele increasing the severity of lung disease. The variant is downstream of the gene EHF, which is also believed to play a role in asthma; the hope is that the function of this gene may shed some light on what causes variation in CF severity. As a CF mutation carrier with a CC genotype, any children that I have would be at a at slightly increased of having worse lung function. However, the variant only explains 1-2% of variation in lung function, so I won’t be worrying too much. [LJ]

A reader got in touch with us to inform of research he is doing into the response of personal genomics customers to genetic information. He is looking for users and potential users of DTC genetic tests to fill out a survey; you can find the survey here. If you have the time, this would be worth doing. Arguments about DTC genetics are too often based on hypotheticals or guesses, but there is a rapidly growing field that looks at how individuals really response to genetic data. This sort of data is exactly what is needed to make sensible decisions about the impact of DTC genetics on society. [LJ]

Continuing her series of interviews with people who have taken genetic tests, Elaine Westwick interviewed Jane Gregory, the mother of a child with a complex developmental disorder that was finally diagnosed by a genetic test. The interview raises a lot of the classical issues that you often see in clinical genetics cases, including the power of finding a genetic cause, even when knowing the cause doesn’t add any new treatment options. Well worth reading. [LJ]

The image at the top of the post, “65 Roses”, was made by Tanya Dawn

Friday Links is a roughly weekly collection of interesting genomics-related links scraped from the interwebs by Genomes Unzipped contributors.

Happy DNA Day! Cambridge members of Genomes Unzipped will be celebrating this evening in traditional British style with a beer or two at The Eagle, the pub in which Francis Crick famously interrupted the lunches of fellow customers to announce that he and James Watson had “discovered the secret of life” (actually the structure of deoxyribonucleic acid, but close enough).

Others are rejoicing in their own way. New York-based “brick artist” Nathan Sawaya, for instance, has built a massive sculpture of the the double-helical model out of LEGO bricks (left). [DM]

23andMe announced yesterday that it will now be releasing information on Alzheimer’s disease risk markers in the APOE gene to customers who purchased their recently upgraded v3 test. The APOE markers are famously associated with a major increase in risk for late-onset Alzheimer’s, with individuals carrying two copies of the ε4 version of the gene being around 15 11 times more likely than average to develop the disease. Customers who have been tested on the v3 platform will be able to able to access their APOE status after “unlocking” it; customers on earlier versions of the test will need to upgrade to get access. You can see screenshots of the unlocking and results pages here. [DM]

Even though genome-wide association studies (GWAS) have identified many loci associated with complex disease, much disease heritability is still unexplained, or “missing”. But what if rather than being missing, some of the heritability was “disguised”. This is the term put forward by Chris Spencer and collegues to describe the proportion of heritability that we miss because SNPs (imperfectly) correlated to the causal variant (“tag SNPs”) are used to estimate explained heritability rather than causal variants themselves. Reassuringly, their simulations show that for the vast majority of loci detected via GWAS the risk estimated from the best tag SNP is very close to the truth. They also show that, occasionally, fine mapping of GWAS loci will identify causal variants with considerably higher risk and this is more likely if the true effect of the locus is large. The figure above, taken from their paper, shows that for estimated relative risks in the range 1.2–1.3, there is approximately a 38% chance that the true relative risk exceeds 1.4 and a 10% chance that it is over 2. The consequence of all of this for personal genomics is that disease risk could be much greater than currently thought for those individuals who, for a given disease, carry a large number of common risk variants. [CAA]

Continue reading ‘‘Disguised’ heritability, changes ahead to marketing of personal genomics, deciphering developmental disorders’

The picture above shows the relatedness of parents across different populations throughout the world; for reference, 0.065 is the average value for a first cousin mating. It comes from a paper out in pre-publication this week at the European Journal of Human Genetics, which estimates the level of inbreeding (or “consanguinity”) of parents by looking for sections of the genome where individuals inherit an identical piece of DNA from each parent. Such “runs of homozygosity” are a sure sign of inbreeding, as both parents will have inherited the bit of DNA from a recent common ancestor: the number and length of these sections can be used to find out how many generations ago the common ancestor lived, i.e. how closely related the parents were (cousins share a grandparent, second cousins a great-grandparent, and so on). In the plot above, we can see a high degree of cousin-marriage in Middle-Eastern cultures, and somewhat more sadly, high degrees of inbreeding in the Native American populations, due to the collapse in their population sizes. [LJ]

For those interested in gene-by-environment interactions the latest issue of Trends in Genetics includes a review article by Carole Ober and Donata Vercelli on the challenges of this area, illustrated by examples from asthma research. In particular they highlight the difficulties of moving G-by-E studies from examination of known candidate genes to genome-wide association. More interactions, this time of the protein-by-protein kind, are the subject of an article by Soler-Lopez et al. in this month’s Genome Research. They looked for interactions relating to Alzheimer disease using a combination of computational and experimental strategies, identifying 66 genes that putatively interact with known AD-related genes. The authors focus on the potential roles of neuronal death regulation and pathways linking redox signalling to immune response in AD pathology. [KIM]
Continue reading ‘Inbreeding around the world, gene-environment interactions and sales of genetic tests’