What I find interesting is how a SNP finding and a blogger can set the press a fire.....especially when the blogger is a junior member of the billionaire's club.
In this case I am speaking of course about Sergey Brin who recently published a blog post on his risk for Parkinson Disease. It helps understand why his wife launched 23andWe......
This research would have great potential if the Company 23andMe would obey the "rules and ethics" of common human research by allowing patients to remove their samples from 23andMe's database if tehy so chose.....and more importantly, consenting a patient when the sample (which 23andMe would now own) would be tested for other things...
23andMe's mission is to be the world's trusted source of personal genetic information
They have a long way to go........
That being said....I think we should talk about LRRK2 and what it means for Sergey and others who carry it. From Sergey
It is clear that I have a markedly higher chance of developing Parkinson's in my lifetime than the average person. In fact, it is somewhere between 20 percent to 80 percent, depending on the study and how you measure," Brin said.
That is 20 percent to 80 percent higher than the average risk......Not 80 percent likelihood to develop Parkinson Disease. That 80% risk is the case for BRCA carriers in breast cancer, but not this LRRK2! This was a statement on his post which some people may get confused by...so don't.
Mr. Brin, who made the announcement on a blog, says he does not have the disease and that the exact implications of the discovery are not clear. Studies show that his likelihood of contracting Parkinson’s disease in his lifetime may be 20 percent to 80 percent, Mr. Brin said.
Parkinson Disease affects approximately 1% of the population by age 65% and 4 to 5% by age 85 years. Therefore the lifetime risk is 2-5%. So a 1.2 to 2.1 Odds ratio would be 4% to 10% roughly. Not 80%!
There are several genes that have been linked to PD, including alpha synuclein, PARKN, PINK1, DJ1 which have all been linked to familial PD. LRRK2 is a realtive newcomer to the field with good publications starting in 2005. For reference the first BRCA publications were in 1994. It took us 10 years to really be able to fully understand and explain what the risks are. We still have problems with this though.
There are several misconceptions about BRCA as there are for LRRK2....worse yet, counseling for LRRK2 can be confusing. Which is why perhaps
Because there are only a small number of genes which are known to have a very substantial effect on health (e.g. 10 times the average risk)
I felt the possibility of discovering something very important to my health was just a hypothetical exercise. So, when my wife asked me to look up G2019S in my raw data (23andMe scientists had had the forethought to include it on their chip), I viewed it mostly as entertainment.....
LRRK2 is not one those genes that increases your risk by tenfold...
LRRK2 mutation accounts for 5 to 6% of familial PD and 1-2% of sporadic PD. Not exactly what I would call useful for a screening test. Mind you this is given for North Americans and Europeans.
These numbers however do change for a few ethnicities including North African Arabs, Ashkenzi Jews where it goes up to 29-37% of familial cases and 7-14% in sporadic....some studies say as high as 41% in sporadics, but the high sporadic data is not replicated.
What is familial PD? Well, at least one first degree relative must carry a diagnosis of PD.
I am not certain of Sergey's Ancestry.....perhaps he is African Arab or Ashkenazi Jewish? That might put his likelihood of having a mutation in LRRK2 higher.....
Interestingly in the largest study of Ashkenaim with PD to date the odds ratio to develop PD was 5.77 which is very high and fairly significant. Unfortunately, these data ONLY apply to Ashkenazi Jews from Israel as this was the population studied.
So don't go thinking it is that high for everyone. In this study, the Odds Ratio for developing PD in Ashkenazi patients with the LRRK2 G2019S mutation was 5.7 (CI 2.8 to 11.7). It is increases when you match age and sex to 8.6. Which has us thinking perhaps this is a sex effect? Not that sex, you perv!
What is the percent of unaffected carriers in the general population of Ashkenazi? 2.2%
That is a scary stat for my Jewish friends. That means this mutation is not nearly as common in the unaffected Ashkenazi Jewish population. This should be only interpreted for this Ethnicity! Not for Europeans or for Americans who do not have Ashkenazi ancestry!!
It was crazy that none of the other mutations in LRRK2 were detected in this Ashkenazi cohort. That certainly speaks for a founder effect!! Similar to the founder mutations in BRCA1/2
In dissecting out thet data a little more we see that the G2019S was found more commonly in Women and in Familial Cases for the Ashkenazi population.
So, I hope that helps. These data and perhaps the numbers Sergey quoted were likely those for Ashkenazi Jews. So if you are Tom Smith from Nebraska, chances are that the LRRK2 data you now could afford to get are not so dire. And even if you are Jewish, the penetrance of this mutation is 24 to 85%
Sergey's post was great and highlights a special issue. Ethnicity and its role in disease. We cannot apply one ethnic groups data to another. A study done on the Chinese does not apply to Northern Europeans. This is why SNP data can mislead and scare.
Here's the big question, when you found out you might get Parkinson Disease Sergey, were you alone? Would have liked to have someone there? Would you have liked to talk with a geneticist? Or was it like Joanna Mountain said to a friend of mine "Aww, Come on, this testing is just for fun"
The Sherpa Says:
At Helix Health of Connecticut, patients are seen that have family history of Parkinson Disease. I believe that all asymptomatic testing of this nature can be confusing and requires appropriately trained consultation....plain and simple. What if Sergey didn't have billions to through at this disease in hopes of a cure and to give him hope? He might be hopeless. In that case he might have even contemplated suicide......in the privacy of his own CPU......