Tag Archives: Population + Epidemiology

Collins: Testimony on the threat of genetic discrimination

The testimony of Francis Collins before the subcommittee on Health is now online

A recent NIH study of families at risk for hereditary nonpolyposis colorectal cancer … revealed that the number concern expressed by participants regarding genetic testing was about losing health insurance, should the knowledge of their genetic test result be divulged or fall into the “wrong hands” … Unless Americans are convinced that their genetic information will not be used against them, the era of personlized medicine may never come to pass. The rest would be a continuation of the current one-size-fits-all medicine, ignoring the abundant scientific evidence that the genetic differences among people help explain why some of us benefit from a therapy while others do not.

Autosomal inheritance of sex-linked marker

While optimizing the analysis strategy for a 500,000 SNP Affymetrix array set, I found 6 autosomal SNPs that show highly significant sex-dependent allele differences: rs2809868, rs4862188, rs2880301, rs3883011, rs3883013 and rs3883014.


Sure, there could be autosomal marker that influences male/female outcome but there is a more likely explanation: All SNPs have paralogue sequence stretches on the Y chromosome that are co-amplified during PCR. From the initial genotyping results it is most likely that only the Y chromosomal stretch is being mutated in SNP 4, 13 and 15.2.

These SNPs are perfect sex marker, as they include an autosomal control allele (in comparison to pure Y markers like SNPs in SRY). They are always unambiguous (in contrast to pure X marker where only heterocygotes are informative).

They even offer advantage to commercial STR kits of the Amelogenin/Amely gene situated (in the Y parautosomal region) as they would not be affected by excess homologous X chromosomal material as often found in forensic situations. In addition, they might overcome some other weakness of the Amelogenin test where a second assay is usually recommended.

If you will ever see a case-control study that is highlighting any of these SNPs, you can be sure that this study had a distorted male-female ratio between case and controls.

More paranormal inheritance

A funny study in PNAS is broadening our view of paranormal inheritance by showing germline chimerism in marmosets:

Using microsatellite DNA markers, we show here that chimerism in marmoset (Callithrix kuhlii) twin … somatic tissue .. found to be chimeric. Notably, chimerism was demonstrated to be present in germ-line tissues, an event never before documented as naturally occurring in a primate. In fact, we found that chimeric marmosets often transmit sibling alleles acquired in utero to their own offspring.

Bad news for all who believe in human paternity testing and 99,999999% probability – and more strange stories (semi-identical twins discovered – hermaphrodite reveals previously unknown type of twinning) at the Nature news blog.

Many, many maps

Ever since I created a linkage map of the human genome with old-fashinoned crimap, we are talking about “mapping” diseases and genes. GIS mapping also ever increases – see the interesting first monday article Many, many maps: Empowerment and online participatory mapping, that has a lot of details about grassroots initiatives building on Keyhole/Google technology. I learned also about Common Census – looks like grassroot epidemiology.

Abstracts that are difficult to understand

Can you find the problem in the following abstract

…We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 times 10-8)…

The BMJ explained last year – why p-values (or relative risks alone) do not make so much sense

Unless ratio measures are reported with the underlying absolute risks, readers cannot judge the clinical significance of the effect. Consider the following example. Readers may be told that the relative risk of death with drug A compared with placebo is 0.5; in other words, people who take drug A are half as likely to die as people who take placebo. But without the underlying absolute risks—the chance of death in each group—the information is incomplete.1 A relative risk of 0.5, for example, is compatible with a wide range of changes in the risk of death: from 20% to 10%, from 1% to 0.5%, and from 0.0004% to 0.0002%.

Open the window

Micro- and macroclimate factors certainly have more influence on our health than being reflected by current research. A new PLOS study now finds that

facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 air changes per hour) … Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free.


Notes on asthma in Africa

I have just found our most recent PLOS paper about asthma in Africa being published online

As of the 1980s, there was an overall conviction that asthma had an anthropogenic origin with indoor and outdoor air pollution as the main culprits. Following some overinterpreted epidemiological findings of the “hygienic” phase, there is now evidence accumulating that the asthma epidemic might have an iatrogenic origin. There might not only be indirect effects of improved living standards and better medical care, there are even direct effects under discussion, for example by oestrogens, vitamin D, antibiotics, and paracetamol. Infant formula (which contains vitamin D) has already entered the food chain in Africa; paracetamol is the most common drug bought over the counter in Ghana. Do African countries offer any unique observations where singular effects of these drugs can be delineated?

An independent review (that I did not know at time of writing) arrived at similar conclusions. We all, however, forgot to mention sensational news as Gambian president Yahya Jammeh can heal asthma clickclick – a more serious appraisal click.

My childhood favorites

My compliments

My compliments to Nicole, the latest Ph.D. student from our lab who succesfully passed her final exam today in Freising at TU München-Weihenstephan. Here is the semi-official document:


The title of her thesis is High-resolution snp scan of chromosome 6p21 in pooled samples from patients with complex diseases , a topic that has recently attracted new interest.

We apply a high-throughput protocol of chip-based mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight; MALDI-TOF) as a method of screening for differences in single-nucleotide polymorphism (SNP) allele frequencies. Using pooled DNA from individuals with asthma, Crohn’s disease (CD), schizophrenia, type 1 diabetes (T1D), and controls, we selected 534 SNPs from an initial set of 1435 SNPs spanning a 25-Mb region on chromosome 6p21. The standard deviations of measurements of time of flight at different dots, from different PCRs, and from different pools indicate reliable results on each analysis step. In 90% of the disease-control comparisons we found allelic differences of <10%. Of the T1D samples, which served as a positive control, 10 SNPs with significant differences were observed after taking into account multiple testing. Of these 10 SNPs, 5 are located between DQB1 and DRB1, confirming the known association with the DR3 and DR4 haplotypes whereas two additional SNPs also reproduced known associations of T1D with DOB and LTA. In the CD pool also, two earlier described associations were found with SNPs close to DRB1 and MICA. Additional associations were found in the schizophrenia and asthma pools. They should be confirmed in individual samples or can be used to develop further quality criteria for accepting true differences between pools. The determination of SNP allele frequencies in pooled DNA appears to be of value in assigning further genotyping priorities also in large linkage regions.

Craving comes from the insula

You may renember the homunculus – a projection of body functions on brain areas. There is an interesting clinical extension stemming from 69 stroke patients of which 15 immediately, easily and permanently quit smoking. One patient said that his “body forgot the urge to smoke”. Sure, this analysis may still be somewhat confounded by the fact that certainly more areas are usually destroyed – but there are interesting approaches that could be followed up, the authors speculate about influencing sensory airway representation, neurotransmitter therapy and monitoring of smoking cessation programs. So stroke may help to quit smoking but I think there are better ways to do that. Seems that Science won this race with Nature. Yea, yea.


Don’t miss the follow up.


Beam me up, Scotty, ….

This is the title of an editorial in The Am J Respir Crit Care Med commenting on current asthma research.
Another editorial in the ERJ asks “The human lung: did evolution get it wrong?”
So I am confused: Did pulmonary science or lung evolution (or both) get it wrong?