#papers overload

Once in a while, I trip over a bunch of interesting articles, and go into a frozen state, unable to decide which one to read or which one to tweet. Today it happened. My solution to escape from this state of indecisiveness is to just list down all the articles, perhaps describe a little bit, and save it for reading some day. It’s likely that “some day” will never come. Yet, at least, I’ll have the memory of stumbling upon these article titles. Such memories will surface back as feelings of deja vu at times when I trip over similar articles again in the future.

A paper in Nature Communications report in detail about the architecture of the trans-ethnic genetic correlations for ~30 complex traits. The authors have adapted the stratified LD score regression framework to partition the trans-ethnic genetic correlations based on various functional annotations. I haven’t had time to read the entire paper, but I managed to glance through the abstract, figures and discussion. One of the findings stood out: the authors show that trans-ethnic correlations (meta-analysed across ~30 complex traits) are significantly lower in genomic regions encompassing genes expressed specifically in skin and immune related tissues. This makes sense as many population specific associations were reported for skin traits and immune diseases, both of which are liable to environmental influences such as sunlight and pathogens. On the other hand, the trans-ethnic genetic correlations are significantly higher for genomic regions encompassing brain-specific genes. This is an important finding because this suggests that it is less likely that we will find any population-specific GWAS associations for brain related traits (e.g. intelligence) and diseases (e.g. schizophrenia). So, all the GWAS loci identified for brain related phenotypes are likely shared across all populations. In fact, the near perfect genetic correlation (rg=0.98) for schizophrenia between East Asians and Europeans aligns with this finding. It is, however, important to note that still the polygenic scores will not be portable across populations because the LD differences between the populations will screw up the polygenic predictions. In a hypothetical scenario, if one is able to experimentally identify the causal variants at all the loci, then perhaps the polygenic scores constructed using only the causal variants might become portable across populations.

Speaking of the devil, another interesting paper in America Journal of Human Genetics (AJHG) reports on the genetic architecture of inflammatory bowel disease (IBD) in 3,418 African Americans (1774 cases and 1644 controls) and how they differ compared to IBD genetics in Europeans. As expected, there seems to be a big difference: out of 241 lead variants identified in Europeans, only 41 replicate, and even among these replicated loci, the effect size correlation was only 0.68 (this poor correlation could be blamed on the LD-differences). Anyways, this paper made me go back to the Nature Communications paper I discussed earlier, and confirm that the tissues with low trans-ethnic genetic correlations include small intestine, colon and ileum. It is great to see that the results from both these papers fit perfectly together. I’ll definitely dive deep into this paper soon.

An another paper in AJHG’s “sister journal” Human Genetics and Genomics (HGG) advances reports a monogenic (sort of) case of ADHD caused due to highly penetrant translocation mutation in CTNND2. I work a lot with ADHD, yet my knowledge on the highly penetrant rare variants causing ADHD is poor. I remember a few large deletion-CNVs causing ADHD, but my mind is blank when I think about ADHD-specific mutations (may be, I always imagined that there aren’t any). So, the words “penetrant attention deficit disorder” in the title pulled my attention. I’d like to read this. Also, studies like this are great examples to demonstrate the genetic component in the etiology of ADHD, which still many people (including doctors!) deny.

A Nature paper reports the role of creatine kinase in the heat generation by brown fat. This paper reminded me of a guest lecture that I attended in 2011 while I was in my first year of my MD at Christian Medical College, Vellore, India. The guest speaker, who is an alumni of our department (I don’t remember the name), spoke about the accidental discovery of the existence of brown fat (or beige fat) in adults while PET scanning adult cancer patients. He presented his molecular research work on understanding the mechanisms underlying brown fat thermogenesis, and how his research findings might help to discover new anti-obesity drugs that can induce brown fat generation in adults. I am curious to know what’s the “big discovery” in the current Nature paper.

An another Nature paper titled “Million-year-old DNA sheds light on the genomic history of mammoths” has come out. Common! Who will not be interested to know what the DNA of mammoths have revealed? Though this is not within my area of expertise, I’m still extremely curious. At least, I’ll read the associated “news and views” article which will be understandable I hope.

An another Nature Communications paper by Peter Visscher and his team has come out. Any paper from Peter Visscher is worth reading, and should be read. No scientists will disagree with me in that, I guess. This paper reports how the heritability estimated by correlating the phenotypic similarity with genetic similarity changes from unrelated individuals on the one end of the spectrum to monozygotic twins on the other. It seems like an interesting paper.

A huge number of genetics papers were unloaded into my twitter timeline. I’ve been looking at these papers like a child looking at the different varieties of candies in a candy shop. My attention kept jumping from one paper to another restlessly. I want to read this. I want to read that. This. That. This. That. I hope to read all these “some day”.

The TOPMED paper is finally--it looks like it has been in review for ever--out in Nature and seems to hold  many interesting contents. I am particularly looking forward to the rare variants section. The abstract reads--“These rare variants provide insights into mutational processes and recent human evolutionary history.“ A quick glance revealed some fascinating analyses, e.g. population differences based on singletons. I always thought singletons mostly represent denovo variants and so have nothing to do with ancestry. Apparently, I am wrong, it looks like. I’ll know when I read the paper.  

A review paper titled “Origins of modern human ancestry“ has come out in Nature, which I learnt from Simon Fisher’s tweet. According to Prof. Fisher, this is a “must read nature paper”. I can’t wait to dive into this.

To celebrate the 20th anniversary of Human Genome Project completion,  Nature has published many ‘news and views’ articles.

1. “Breaking through the unknowns of human reference genome”

2. “From one human genome to a complex tapestry of ancestry“--this is so exciting.

3. “Sequence three million genomes across Africa“--what? did you say 3 million?

4. “A wealth of discovery built on the Human Genome Project — by the numbers“--amazing visualizations!

5. “How the human genome transformed study of rare diseases”

6. “The broken promise that undermines human genome research“--very important article, which talks about data sharing and importantly, data hoarding.

Another paper in NPJ genomic medicine reports the association between of amylase copy number genes and adiposity traits. I am very much looking forward to read this. I have a long history with amylase copy number variants, which itself will require a separate post.