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.
Ion channels are pore-forming proteins that poke through cell membranes to control the movement of ions like calcium, potassium, and chloride in and out of cells. Movement of these ions is critical for a wide-array of physiological processes — everything from controlling the heartbeat to flexing muscles to firing neurons.
Because ion channels are so essential, mutations in these proteins can lead to serious disease. For example, cystic fibrosis is caused by mutations in a chloride channel protein and certain forms of epilepsy are caused by mutations in sodium channel genes.
Three studies published online yesterday in the journal Nature Genetics show that common variants in ion channel genes may also contribute to disease risk. Two groups found evidence that a potassium channel protein is associated with type 2 diabetes, while another group discovered that a calcium channel and a protein that regulates sodium channels might be associated with bipolar disorder.
Type 2 Diabetes
Of all the conditions that have so far been studied with genome wide association study methods, type 2 diabetes has been one of the blockbusters. The 23andMe Gene Journal (now called Health and Traits), for example, features 9 SNPs that have been repeatedly associated with the disease in European populations (there are 3 for Asians and 1 for Africans). Research continues and SNPs are constantly being found and/or validated.
This SNP is in KCNQ1, which encodes part of a potassium channel that has known roles in cardiac muscle. It is not yet known how this gene could affect the risk for type 2 diabetes, but there is evidence that it is turned on in the pancreas. Yasuda et al found that people with the CC version of this SNP had evidence of impaired insulin secretion. Another potassium channel gene, KCN11 has previously been associated with type 2 diabetes in several studies.
Genomewide association studies have struggled to find SNPs that are associated with diseases in more than one ethnic group. That’s why it is surprising that rs2237892 was associated with type 2 diabetes not only in the original Japanese set of cases and controls used in this study, but also in Chinese, Korean, and European samples.
When the data from all groups studied were combined together, each C at rs2237892 increased the odds of type 2 diabetes by 1.4 times, compared to the TT genotype. It’s important to note, however, that the C version is actually pretty common.
In Asian populations, the C version of rs2237892 increased a person’s odds of type 2 diabetes by 1.42 times compared to people with TT. But because about 50% of the Asian population is actually CT at this SNP, it could be viewed that CC has 1.3 times the odds compared to typical, while TT has 0.61 times the typical odds.
In European populations, about 85% of people are CC. This means that the results of Yasuda et al really show that compared to most Europeans, people with CT at rs2237892 have 0.78 times the typical odds of developing type 2 diabetes, and the odds for people with TT are 0.52 times typical.
Unoki et al, publishing at the same time in Nature Genetics, found similar evidence for SNPs closely related to rs2237892 in the same gene in both a Japanese and a Dutch sample.
Bipolar disorder is a serious mental illness that affects about one to three percent of the world’s population. As with many other common diseases, researchers have been using genomewide association studies in an effort to find SNPs associated with bipolar disorder in order to begin to understand how and why this disease strikes and how best to treat it. So far, however, progress has been slow and there has been little agreement from study to study.
In their quest to tease out the genetics of bipolar disorder, Ferreira et al took an approach that is becoming more popular–they combined data from several smaller studies to get the larger sample size that is often needed to find variants with modest effect. In total, they looked at 10,596 people of European ancestry – 4,387 people with bipolar disorder and 6,209 controls.
Two SNPs stood out as candidates for bipolar disorder. Both were in genes related to ion channels.
(The original SNPs, rs1006737 and rs10994336, are not on the 23andMe platform. Here we give data for proxies of the original SNPs – rs2159100 and rs4948418)
The first SNP is rs2159100 in CACNA1C, which encodes a calcium channel. Previous studies had hinted that this gene might be associated with bipolar disorder. Each T at this SNP increased the odds of bipolar disorder by 1.18 times compared to having two CC copies.
The second SNP was rs4948418 in ANK3. This gene encodes a protein that has been shown to regulate sodium channels. Each T at this SNP upped the odds of developing bipolar disorder by 1.45 times compared to the CC genotype.
Further evidence for the involvement of these SNPs in bipolar disorder comes from previous studies by these same researchers. In mice they found that lithium, the most effective drug for treating bipolar disorder, appears to decrease the amount of protein made by the ANK3 and CACNA1C genes.
“Finding statistically robust associations linked to two proteins that may be involved in regulating such ion channels – and that are also thought to be targets of drugs used clinically to treat bipolar disorder – is astonishing,” said Pamela Sklar, a lead author of the study, in a statement.