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Previously in The Spittoon, we discussed two papers that identified genetic variants associated with hemoglobin levels in circulating blood.
But blood consists of much more than hemoglobin, and it is responsible for much more than just transporting oxygen. This week Nature Genetics published the results of two of the largest blood studies to date, which together identified dozens of new variants associated with nine blood-related traits.
In addition to red blood cells, which carry hemoglobin, whole blood contains white blood cells—a crucial part of our immune system—and platelets, which are important for clotting. All of these cellular components are suspended in a protein-rich plasma that makes up most of the volume of blood, and maintains the pressure needed to deliver the blood’s cargo throughout a person’s body.
Like hemoglobin levels, measurements of other blood traits can be informative about health. An abnormally high white blood cell count and platelet volume have both been linked to an increased risk for heart attack. These measurements can also indicate the presence of infectious disease, immunological disorders or cancers.
Nicole Soranzo and her colleagues in the HaemGen consortium measured hemoglobin concentration (Hb), red blood cell count (RBC), red blood cell volume (MCV), platelet count (PLT), platelet volume (MPV), white blood cell count (WBC), the amount of hemoglobin per red blood cell (mean corpuscular hemoglobin content, or MCH), and the amount of hemoglobin relative to the size of the cell (mean corpuscular hemoglobin concentration, or MCHC) in more than 14,000 healthy individuals from Europe. They found sixteen new genetic associations with blood traits from fifteen genomic regions not previously thought to be involved.
Santhi Ganesh and her colleagues in the CHARGE consortium measured Hb, MCV, RBC, MCH, MCHC, and the percent of red blood cells in whole blood (hematocrit, or Hct) in more than 24,000 Caucasian individuals from the U.S. and Europe. Here, they found nine new associated variants from eleven previously unassociated genomic regions.
(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service using the Browse Raw Data feature. See table at the end of this post.)
One of the advantages of these studies is the number of traits that they analyzed.
“Until now, few genome-wide association studies have looked beyond single traits,” Soranzo’s co-author Christian Geiger said in a press release. “But, through a systematic analysis of correlated traits we can begin to discover such shared genetic variants, forming the basis for understanding how these processes interact to influence health and disease.”
Both teams noted several genomic regions that play a broad role in blood-related health. The HBS1L-MYB, TFR2-EPO, TMPRSS6 and HFE regions were all associated with at least three different traits. These regions have also been connected to fetal hemoglobin levels and the iron-overload condition hemochromatosis. Of these newly associated variants, many are close to genes that present promising candidates for further research.
Soranzo’s team went further by investigating whether two of the variants associated with increased platelet volume (PLT) rs11066301 and rs11065987, were also associated with coronary artery disease. They analyzed these SNPs in about 9,500 people with coronary artery disease and 10,500 healthy controls. They found that at both SNPs, each copy of a G increased odds of coronary artery disease by about 1.15 times.
(23andMe customers can see their data for rs11065987 by using the Browse Raw Data feature. 23andMe does not report on rs11066301, but we do report on rs11066320, which correlates perfectly with rs110066301. For rs110066320, the A allele corresponds to increased PLT and higher odds of coronary artery disease.)
When the researchers looked more closely at the region where rs11066301 and rs11065987 are located, they found a block of ten SNPs that tend to be inherited together, and which are all associated with increased PLT and risk of coronary artery disease. They also confirmed previous findings from other researchers of association between celiac disease and type 1 diabetes with SNPs in this block.
Data for chimpanzees and multiple human populations point to a relatively recent event in human evolution where the above-mentioned genetic variants swept across European populations — but not East Asian or African populations. Because the block of SNPs is located in an area of the genome involved in immune response, the authors suggest that these mutations may have given some populations a survival advantage against infection, despite increasing the risk for certain diseases.
SNPs associated with blood-related traits
|rs1800562||A||Increase MCV and Hb||Located in HFE region|
|rs11065987||G||Increase PLT, decrease Hct||Also increases odds of CAD|
|rs11066320*||A||Increase PLT||Also increases odds of CAD|
|rs10480299*||C||Increase Hb, Hct|
|rs855791||A||Decrease Hb||Located in TMPRSS6 region|
|rs9494145*||C||Increase Hct, RBC||Located in HBS1L-MYB region|
|rs4820268*||G||Decrease Hct, MCH, MCV||Located in TMPRSS6|
|rs9399137*||C||Decrease MCH||Located in HBS1L-MYB|
|rs4895441||G||Decrease MCV||Located in HBS1L-MYB|
* In some cases, 23andMe does not cover the original SNP, so a proxy SNP that correlates perfectly with the original in Europeans is reported instead.
SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.