Thursday, December 18, 2014

CardioGxE analysis would not be so rich without the help of students

In late October we published a paper on a catalog of cardiometabolic gene-environment interactions pulled from over 380 publications. That paper is entitled "CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits" and represents, among many other aspects of my research, the benefit and satisfaction of giving first-year nutrition graduate students the opportunity to engage in research and contribute important results to a larger research effort.

Lately, I have had several opportunities to guide students of the Tufts Friedman School of Nutrition Science and Policy during a practicum or directed study. I often try hard to find a project that will contribute directly to something we have ongoing that also has good potential to be published in the near future. That does not always come to be, but for our CardioGxE paper such was the case. Four of my co-authors were first-year grad students, and another three were more senior. Particularly for these four younger students, they each made unique and important contributions to the analyses we present in the paper. Our paper would not have the impact it is currently enjoying nor be as complete in showing the utility of gene-environment interactions without their work. Thank you to you all!

Which brings me to my main point: Consider well the abilities that a group of students can bring to your project. Engaging them as equals, as true colleagues, could very well facilitate a project's completion and publication. And, if those students are now authors, say on their first paper, that makes it very nice all around.

Tuesday, September 9, 2014

NuGO Week: Mediterranean diet and the Nordic diet

Yesterday began the 11th NuGO Week conference on “Nutrigenomics of Food” with a debate on Mediterranean diet and the Nordic diet. The Mediterranean diet (MD) is well known if not precisely defined - little to no dairy in Spain, but feta and other cheeses in Greece. We heard of results from PREDIMED and the view from Spain. The Nordic diet (ND) is a contemporary adaptation of healthy and traditional food choices from Nordic countries.

Both diets show health benefits in the respective examined populations. These benefits were described as mainly pertaining to cardiovascular disease, including glycemic measures, and to chronic inflammation.

What we heard was much more compare and contrast (of data) than a debate. There was only very brief mention of conducting the same experiment for both diets (a metabolomics assessment of blood and urine from subjects taking the diet of the respective area (Spain and Norway, e.g.). But no one offered putting Spaniards on a Nordic diet and Norwegians on a Mediterranean diet.

One thing I will like to see is an analysis of the response to the MD in PREDIMED based on an analysis of the genetic ancestry of the individuals. There are sufficient data to be able to classify the subjects by genetic ancestry along norther-southern European axes. Then, we can address if those persons with greater northern European ancestry show a weaker or equal beneficial response to the MD. 


Similarly, the ND projects would do well to engage more subjects - although I fully realize that the population of Spain is likely larger than that of all five Nordic countries combined - and incorporate genetics and other large data sets.

NuGO Week: Mediterranean diet and the Nordic diet

Yesterday began the 11th NuGO Week conference on “Nutrigenomics of Food” with a debate on Mediterranean diet and the Nordic diet. The Mediterranean diet (MD) is well known if not precisely defined - little to no dairy in Spain, but feta and other cheeses in Greece. We heard of results from PREDIMED and the view from Spain. The Nordic diet (ND) is a contemporary adaptation of healthy and traditional food choices from Nordic countries.

Both diets show health benefits in the respective examined populations. These benefits were described as mainly pertaining to cardiovascular disease, including glycemic measures, and to chronic inflammation.

What we heard was much more compare and contrast (of data) than a debate. There was only very brief mention of conducting the same experiment for both diets (a metabolomics assessment of blood and urine from subjects taking the diet of the respective area (Spain and Norway, e.g.). But no one offered putting Spaniards on a Nordic diet and Norwegians on a Mediterranean diet.

One thing I will like to see is an analysis of the response to the MD in PREDIMED based on an analysis of the genetic ancestry of the individuals. There are sufficient data to be able to classify the subjects by genetic ancestry along norther-southern European axes. Then, we can address if those persons with greater northern European ancestry show a weaker or equal beneficial response to the MD. 


Similarly, the ND projects would do well to engage more subjects - although I fully realize that the population of Spain is likely larger than that of all five Nordic countries combined - and incorporate genetics and other large data sets.

Wednesday, July 30, 2014

Genetic pedigree symbols and legend

The following has been making the rounds on Twitter the past few days. In order to make this useful information available to more viewers and for a longer time, I decided to post this here.


Thursday, April 3, 2014

ARAP1 and type 2 diabetes - a circadian connection?



A new report in the American Journal of Human Genetics shows a variant with association to type 2 diabetes and insulin levels functions within an allele-specific motif for islet cell transcription factors PAX4 and PAX6. Specifically, "measurement of allele-specific mRNA levels in human pancreatic islet samples heterozygous for rs11603334 showed that the T2D-risk and proinsulin-decreasing allele (C) is associated with increased ARAP1 expression (p < 0.02). We evaluated four candidate functional SNPs for allelic effects on transcriptional activity by performing reporter assays in rodent pancreatic beta cell lines. The C allele of rs11603334, located near one of the ARAP1 promoters, exhibited 2-fold higher transcriptional activity than did the T allele (p < 0.0001); three other candidate SNPs showed no allelic differences. Electrophoretic mobility shift assays demonstrated decreased binding of pancreatic beta cell transcriptional regulators PAX6 and PAX4 to the rs11603334 C allele."

Interestingly, Pax4 is abundantly over-represented within cis-regulatory motifs in mouse clock-controlled genes, in liver and muscle, per Table 1, and relative to peak Per2 expression in mice, the Pax4 protein recognizes a motif over-represented in the suprachiasmatic nucleus (SCN, the "master clock" in the brain) at phase 12, per Table 2. These data are from Bozek, Relogio, et al 2009 PLoS One4:e4882. That same study showed similar activity for Pax6: relative to peak Per2 expression in mice, Pax6 protein also recognizes a motif over-represented in the SCN at phase 12, per Table 2 (Bozek Relogio 2009 PLoS One 4:e4882, PMID 19287494).

This makes one wonder about the timing of the food intake that might exacerbate glucose homeostasis in carriers of the risk allele.