Wednesday, December 19, 2012

Cystic Fibrosis Improved Screening

In the first post I claimed that like Tay-Sachs in Israel Cystic Fibrosis could be drastically reduced with some relatively inexpensive genetic testing. In the second further analysis suggested that such genetic screening of the Irish population would pay for itself several times over. In this post I want to see if some form of targeted screening could be shown to be as cost effective as currently implemented screening.

Currently there is free screening for people who has relatives with CF and their partners. I assume they include second cousin as a relative. Based on this paper and some consanguinity calculations I calculate that an Irish couple with one of their second cousins has CF have about twice the chance of having a child with CF as the general population. This means you can be tested for free currently if you have about a 1 in 700 chance of having a child with cystic fibrosis whereas the general population with a 1 in 1444 chance. If a test can be focused the test so that it is twice as good as random screening that should be enough by current standards to be rolled out.

How could a non random screening be made this focused?

1. Geographic area. Some areas of the country might be more likely to have CF carriers than others. Targeting screening in these areas might make it twice as effective. The Cystic Fibrosis Registry of Ireland annual report 2010 gives numbers for Irish counties. 4 counties do not have their numbers listed but I have estimated these based on their population.

This map is based on the figures of people with CF found in the registry. This could be a biased sample or people could have moved. A better measure would be babies born with CF in each county.

Number of people with CF in each county might be useful for deciding how to allocate some treatment resources. What % of people have CF is more interesting for screening though. To work this out we first need the numbers found in each county.

The number of people with CF in the registry per ten thousand people is

I can send anyone who wants them full sized versions of these maps or the r package code I used to generate them. The code I used is below

con <- url("")
people<-read.csv('cases.csv', sep=',', header=TRUE)
pops = cut(people$cases,breaks=c(0,2,10,20,30,40,50,70,150,300))
spplot(gadm, "pops", col.regions=myPalette, main="Cystic Fibrosis Cases Per County",
       lwd=.4, col="black")
dev.print(file="CFIrl.jpeg", device=jpeg, width=600)
population<-read.csv('countypopths.csv', sep=',', header=TRUE)
pops = cut(population$population,breaks=c(0,20,40,60,70,80,100,160,400,1300))

spplot(gadm, "pops", col.regions=myPalette, main="Population in thousands",
       lwd=.4, col="black")
dev.print(file="PopIrl.jpeg", device=jpeg, width=600)

gadm$cfpop <- people$cases/(population$population/10)
cfpop = cut(gadm$cfpop,breaks=c(0,0.5,1,1.5,2,2.5,3,3.5))
gadm$cfpop <- as.factor(cfpop)

spplot(gadm, "cfpop", col.regions=myPalette, main="CF/Population Irish Counties",
       lwd=.4, col="black")
dev.print(file="CFperPopIrl.jpeg", device=jpeg, width=600) 
If this result was replicated in a more complete analysis just picking the darker counties could get you the two times amplification needed to have a test as strong as the currently paid for ones.

2. Pick certain ethnic minorities. Some groups have higher levels of CF than the average population. For example travellers have higher levels of some disorders. 'disorders, including Phenylketonuria and Cystic fibrosis, that are found in virtually all Irish communities and probably are no more common among Travellers than in the general Irish population. The second are disorders, including Galactosaemia, Glutaric Acidaemia Type I, Hurler’s Syndrome, Fanconi’s Anaemia and Type II/III Osteogenesis Imperfecta, that are found at much higher frequencies in the Traveller community than the general Irish population'. 'There is no proactive screening of the Traveller population no more than there is proactive screening of the non-traveller Irish population'. I do not think deliberate screening of one ethnic group, unless that group themselves organise it, is a good idea. Singling out one ethnic group for screening risks stigmatising its members and reminds many of the horror of eugenics.

3. Certain disorders seem to cluster with CF. 'In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis'. Ireland also has the highest rate of celiac disease in the world (about 1 in 100). If CF and celiac disease or some other observable characteristic are also correlated in Ireland testing people with celiac disease in their family could also provide amplification of a test.

4. Screening parents undergoing IVF. HARI was the first clinic in Ireland to offer IVF and it currently receives up to 800 enquiries a year specifically about the procedure. It carries out over 1,350 cycles of IVF treatment annually and over 3,500 babies have been born as a result. The Merrion Clinic carries out up to 500 cycles of IVF per year, while last year, SIMS carried out 1,063 cycles." IVf is roughly 33% effective per cycle so this means about 1000 children are born through IVF from these three Irish clinics here each year. Screening of these parents would prevent roughly one CF case per year. Screening people who use IVF does not prevent many cases. It can be used by people who know they are CF carriers to avoid having a child with CF though.

Concerns about the privacy and security of a general genetic screening program of the Irish population should not be ignored. Cathal Garvey on twitter pointed out that this screening would require 'With explicit informed consent & ensuing destruction of samples, Just wary of prior shenanigans of HSE bloodspot program. i.e. it's already fashionable among governments to abuse screening programs to create 'law' enforcement databases. Without clear guarantees against that, must weigh the costs of mass DNA false incriminations vs. gains of ntnl screening prog!' I agree that any genetic screening program for Ireland would have to ensure privacy for the individual.

Screening the general population for carriers of serious genetic disorders would save money and suffering. If the level of savings are not sufficient for general screening focusing on certain locations or relatives of people who suffer from disorders that co-occur with CF could amplify the returns sufficiently to be as useful as current screenings.


David R. MacIver said...

I don't have anything useful to add, but just wanted to say thanks for writing these. I've been finding it a really interesting insight into a problem I had no idea existed.

Anonymous said...

There is voluntary screening in place for couples where one of them has CF; they test if the other is a carrier. If only one person in the relationship has CF and the other is not a carrier of the gene, then the chances of having children with CF is the same as for parents who both are not carriers. Basically its the same chance about 1 in 450 (approximately). So screening embryos during IVF treatment would be another layer that would certainly help.