 Great, I'd like to thank the organizers for the opportunity to be here to honor and a privilege to be here today I'm going to talk about we've talked a lot about ancestry and I want to talk about The medical importance of antrocessory and I'm going to use an example that we studied for years, which is asthma When you look at the demographics of the United States is drastically changed in fact the minority is now becoming the new majority and this is actually quite relevant for all the topics that We've been discussing because when you look at all contemporary genetic studies done up until in 2011 The vast majority have been done in Caucasian populations 4% is represented by non Caucasian populations and this is a problem This is the problem that causes me great distress because the NIH is federally funded by taxpayers You me yet large swaths of our population are not benefiting from the the tremendous advances of the genomic genomic revolution and It's more problematic to me as a physician when you look at differences in disease disparities This is asthma in the United States and you can see that asthma varies Traumatically by race or ethnicity, whatever you want to call it. This is as a prevalence highest in Puerto Rican's lowest in Mexicans 90% of funding goes to study Caucasian populations and you might say well Maybe it's Puerto Rican's complain a lot and they don't really have asthma. This is artificial. It's a bias But when you look at death rates again, you see it high highest of Puerto Ricans highest in African Americans and to me, this is a travesty. These are kids. This is Asmortality in children. No kid in the United States should die from asthma Okay, so There are multiple factors that could help to explain this environmental factors social factors access to care But we asked the question whether or not genetic factors helped explain this So in order for us to get a good handle on this we had to have Quantifiable and reproducible measures of asthma severity and one of the ways that we did this has had all these kids Thousands of kids that we've measured throughout the United States Perform was called spirometry lung function testing any one of you who has any sort of pulmonary disease will go to a clinic And you'll get this test done here. We have a individual who's Puerto Rican He's breathing into machine and we get this nice output this flow curve this what we call a flow volume curve and What it tells us is how tight your airways are and by high Tight your airways are dictates how much you breathe obviously if they close if your earwars closed down you can't breathe and you die So we did this test to thousands of kids and we got this measure and the measure that we're gonna focus on is this What's called FEV one at the top there. It's just a proxy for how tight your airways are now in order to do that we have to have a reference and Whether you guys know it or not and we talk a lot about race and how much people don't like race and so forth When you walk into a clinic some clerk is looking at you and Assigns race to you whether you know it or not And if you walk into a pulmonary clinic that I run and I direct and I see thousands of kids The admin person who may not know anything about anthropology history or genetics whatever Has to sign a race to you and then the technician compares you to what is called national data And these are national data that are funded by the federal government in which they measured lung function in thousands of people kids adolescents adults men and women and they that were Quote-a-quote healthy and they became our reference equation and what you see here and I modified the national data slide to show that on the In green we have African-Americans on the left In pink we have Mexicans and in Caucasians We have blue on the left bar the higher that FEV one value the Better your lung function the lower it is the lower your lung function And on the bottom curve going from left to right is age and so you can see that It's true life goes downhill after 25 but But I still got it, but you may you may not but the important thing is that there are racial differences in Our lung volumes. Okay, so that's that's actually very important So you get your lung test and then you're gonna be compared to this and basically it's a pull-down menu And it's all based upon mathematical algorithms But one of the things that's important is what you are classified as white black Or Mexican if you're Indian you're gonna be classified as white if you're Chinese you're gonna be classified as white I'm sorry. There's no reference equations for y'all so When we studied African-Americans And I was sitting in the clinic. I I was asking myself Well, God African-Americans are racially or or ancestrally mixed and this is a sample from our own data in which we use Gene chips a million genetic markers to estimate African ancestry in Individuals that said all four grandparents were African-American Okay, and then we just lined them up. I've ranked them. So each bar represents an individual so going from left one to a hundred Green being African Yellow being European ancestry we can see that there's a gradient of Increasing amounts of African ancestry amongst individuals all of whom said all four grandparents were African-American so that's that makes it complex because when Obama comes to my clinic and Asked for long function test. I don't know what the hell to do Is he white or is he black and that's important Do we compare him to the white reference equations or do we compare them to the black? So I was perplexed by this and so so what we did is We asked this question. Do we do Assigned racial categories or whatever you guys want to call it ethnic categories or do we use genetic ancestry? I Was really at a conundrum there. So what my colleagues and I and these are all friends of mine that work together that I've trained We asked the question what how does it relate to spirometry? And this is really really cool What we found was this It's a complex slide But I'll explain it on the left axis We have the severity of your lung disease what we call FEV one again The higher the value the better the lower the value the more severe your disease or the smaller Your lung function is on the bottom curve going from left to right We have increasing amounts of African ancestry and what we demonstrated is that with increasing amounts of African Ancestry that you had lower lung function or more severe disease We did this in a sample called cardiac that included about 800 individuals we went on to replicate this in three national study populations of African Americans and Subsequently published it in a New England journal and what it does is it tells us that When when we take an individual an average male for example who might be five eight good-looking like me And well, I'm not sure what I am African American Hispanic or Native American But if we put plug them into the standard reference equation if they're a Caucasian we get an estimated value of say four point six liters But if we do the pull down for African Americans, we get an estimated normal value of 3.9, but what you can see is that Dependent upon where your ancestry is If you're a bomb in your 5050 you'd be right there in the clifters other work So you'd be right in the middle we'd underestimate your amount the amount of lung disease Obama has But if you're have greater than 90% African ancestry We'd overestimate and this is a problem We demonstrated by including genetic ancestry into the model that determines Normal values of lung function we can improve the accuracy of the test by 15% That is huge and why is it important to you? Why should you care? Well, I'll tell you in a second But one of the things that we did is we built the largest Pediatric minority study of asthma in the United States. We have over 9,000 children They're all in my lab. It's taken years to do this We perform lung function testing in all the children that had asthma We had a political group in sites all over the United States Puerto Rico and Mexico and what we found led by one of my star postdocs Probably one of my best postdocs Maria Pinoyana's from the Canary Islands. She demonstrated again amongst Hispanics That with increasing amounts of African ancestry that we have lower levels of lung function And this is fantastic because because we said I did the study and I was trained as an epidemiologist I knew how to do a proper study. We went and we not only were able to look at ancestry, but we were able to look at Involved we measured environmental factors. We measured air pollution We just published the largest air pollution study of asthma in minority children in the United States Over 7,500 children. We were able to adjust for smoking in uterus smoke other so other environmental factors that might co-vary or influence lung function and We are also able to adjust for socioeconomic factors Income education insurance discrimination and acculturation and despite all these potential confounders We we knew which influenced lung disease We still saw a very strong association with ancestry and lung function and that was cool What it suggests though and where we're going is that there's something that co-varies with genetic ancestry And it's probably a gene that's specific to African populations that influences lung disease So this is work in progress. This paper was just under review at the New England Journal We're going to get to it. We're going to identify the gene that helps to explain this association But it's something that tends to be population specific. Now Why should you care? Because we have clinical standards that are Dictate how you get treated how you outcomes We have clinical reference values for lung function. We define them as FEB 1 and FEC and Dependent upon where you are at with respect to those clinical standards If you're if there's as much as a 15% iterate it could put you on one side of the the Beneficial curve or it could put you on the other side of the negative side of the curve It affects disability ratings lung transport plant referrals Preoperative risk and I'll tell you a little story that really inspired me. I had a firefighter Who is on the job? African-american had smoke inhalation smoke inhalation damages your lungs on the job in injury The firefighter has an incentive to get some sort of disability compensation The insurance company has an incentive not to pay So the fire so they sent him to me as a third independent party to evaluate this guy's lung disease Well depending upon how much African ancestry he has He can either have a 15% error rate and either benefit qualify for disability benefits But he can also have a 15% error rate in the other direction and not qualify And so this was a nice advance in clinical care And this is why I got accepted to the New England Journal of Medicine Because we prove that by including genetic ancestry That we can improve upon clinical standards and actually improve care for all populations This one happens to be relevant for African-americans, but we did the same thing for Hispanics and we're working on developing normal pulmonary reference equations for other populations That are like I said Indians Asians and Puerto Ricans have no reference equations But anyway, I'm not naive We recognize that disease and health are Dictated by social factors probably the biggest determinant of health is a soul in our social factors Social economic status Environmental factors we know that access to care where I work at a work at a county hospital So general access to care is a very important determinant of Health, but we've also demonstrated that ancestry which modifies genetic factors There are gene-gene interactions that also influence health and that collectively if we're going to need that if we do proper studies We're going to need to take this very comprehensive Multidisciplinary approach to do this and that's what we've been trying to do for the last 12-15 years Anyway, I'd like to thank my team Much of the work was led by the folks out here on the left and my clinical collaborators on the right And I'd like to thank you guys for again the opportunity to present and also thank you for listening There will be opportunity for questions later. I'm going to introduce our next speaker Professor Chakravadi from Hopkins He's one of the original pioneers in terms of sequencing the human genome so he was had this wonderful idea early on that Understanding our genome is going to help us in terms of health and human history. So he's here to tell us the story