Thank God the British are working on South Asian genomics

The sequences of 150,119 genomes in the UK Biobank:

We defined two other cohorts based on ancestry: African (XAF; n = 9,633; Extended Data Fig. 4) and South Asian (XSA; n = 9,252; Extended Data Fig. 5) (Fig. 3a–c). The 37,598 UKB individuals who do not belong to XBI, XAF or XSA were assigned to the cohort OTH (others). The WGS data of the XAF cohort represent one of the most comprehensive surveys of African sequence variation to date, with reported birthplaces of its members covering 31 of the 44 countries on mainland of sub-Saharan Africa (Extended Data Fig. 4). Owing to the considerable genetic diversity of African populations, and resultant differences in patterns of linkage disequilibrium, the XAF cohort may prove valuable for fine-mapping association signals due to multiple strongly correlated variants identified in XBI or other non-African populations.

Nearly 10,000 South Asians at high-quality whole-genome sequence scale is nice to see. Obviously, this is oversampling some groups (Mirpuris, Syhletis, and East African Indians who are mostly Guju), but it’s better than nothing. It’s really sad that the British are pushing forward with this. The Chinese have started to move into sequencing their whole nation (they have millions at low coverage). This isn’t that expensive; less than $100 per person at scale. Why is India tarrying on this? I don’t have inside info but I think the Permit Raj strikes again.

Start-up Ecosystem In India

Maneesh has a freewheeling conversation with Roshan Cariappa, founder and host of the Start-up operator podcast, on the start-up ecosystem in India.

The conversation encapsulates ‘ Dummies guide to Indian start-ups’, covers the industries and the geographies that make up for this space and ends with opportunities and challenges that abound.

 

@maneesht and @roshancarippa on twitter.

Podcasts on the Indian start-up ecosystem:

The Startup Operator Podcast: https://www.startupoperator.in/

Indian Silicon Valley Podcast: https://airtable.com/shrTOFf1z5UT0q9p8

VCPreneur: https://thevcpreneur.com/

The Indian Dream: https://www.theindiandream.in/

 

 

Indo-Turks and Anglo-Normans

Posting after a while, as this topic is very BP and I managed to write a rather long Twitter thread on it. So just compiling it all here in a neater format. May revisit and clean it up further later.

A short piece on why the Islamo-Turkic colonialism in India is not the same as the experience of the English who were colonized at roughly the same time by the Francophone Normans. Note Mahmud Ghaznavi died in 1030 / William Duc de Normandie was born in 1028.

Continue reading Indo-Turks and Anglo-Normans

The Indian migration to Southeast Asia

Ancient DNA from Protohistoric Period Cambodia indicates that South Asians admixed with local populations as early as 1st-3rd centuries CE:

Indian cultural influence is remarkable in present-day Mainland Southeast Asia (MSEA), and it may have stimulated early state formation in the region. Various present-day populations in MSEA harbor a low level of South Asian ancestry, but previous studies failed to detect such ancestry in any ancient individual from MSEA. In this study, we discovered a substantial level of South Asian admixture (ca. 40% – 50%) in a Protohistoric individual from the Vat Komnou cemetery at the Angkor Borei site in Cambodia. The location and direct radiocarbon dating result on the human bone (95% confidence interval is 78 – 234 calCE) indicate that this individual lived during the early period of Funan, one of the earliest states in MSEA, which shows that the South Asian gene flow to Cambodia started about a millennium earlier than indicated by previous published results of genetic dating relying on present-day populations. Plausible proxies for the South Asian ancestry source in this individual are present-day populations in Southern India, and the individual shares more genetic drift with present-day Cambodians than with most present-day East and Southeast Asian populations.

No surprise to readers of this weblog. South Asians obsess about possible admixture/contact with West Asia and Europe for obvious reasons, but it’s been pretty clear for a while that the “Indian cultural influence” on Southeast Asia was also demographic. Mainland Southeast Asia and the western part of Maritime Southeast Asia have minor but consistent levels of Indian ancestry. It showed up decades ago in Cambodian males who carried R1a Y haplogroup. And it showed up in a 2012 methods paper that detected gene flow from Pakistanis to Cambodians (no Indian samples in the dataset):

Genetics is basically done now. You can observe, for example, that lowland Thai populations have Indian ancestry, while highland tribes don’t have it.

We now know that the influence of Indian culture of a southern flavor to Southeast Asia was mediated by large numbers of humans. Indian genetic imprint on Burma can be chalked up to being Bengal’s neighbor, but you can’t say the same about Cambodia or Bali. Who were these people? Well, in a way, you could say that they were the “Brown Rajahs” for ancient Sarawak…

Farewell, Houston

Farewell, Houston

I arrived in Houston because of an email. I had just gotten done with my USMLE step one in July 2016 and was furiously emailing people in the U.S. for possible observer-ship opportunities. I did not get a lot of replies. Almost a week after I had started this process, I got an email from a famous pathologist at M.D. Anderson Cancer Center (MDA) in Houston. It was brief and to the point. He wrote that he can accommodate me next year in April. I was over the moon. Prior to this episode, I had never been to Houston or known anyone from the city, except a professor of history at Rice University.

I arrived in Houston in April 2017 after spending some time doing observer-ships and studying for USMLE step two, in West Virginia and Miami. It wasn’t as hot as I had expected it to be and in my initial encounters, I found people to be generally friendly and warm. Houston wasn’t culturally impenetrable as Miami or as distant as West Virginia. It was a city teeming with people who looked like me, with huge hospitals and endless roadways. I had booked an Airbnb for my first two weeks of stay and then moved to a private room I had rented from a very interesting character named Gustavo (Gus). I met Gus through a random mutual friend on Facebook, a Pakistan-American girl who had added me as a friend after some of my work on environmental issues in Pakistan. She was renting from Gus at a different location and got me in contact with him. I spent two months at MDA, left for three weeks to visit Pakistan, and returned to the Houston area. While I was at MDA, I met a resident from the University of Texas Medical Branch in Galveston who got me intrigued about the program and I met the Chair of the program who was welcoming. Afterward, I was in Galveston for the next three years, firstly to do research or get observer-ship at the medical school there (didn’t get either) and later, for residency training at the same medical school. Two years into my residency (total of four years), we moved to the clear lake/NASA suburb of Houston, and another two years afterward, out of Houston for good, for my fellowship.

It was a tough decision to leave but after a lot of brainstorming and weighing options, I felt it best to leave the area. There were many things that I like in Houston and a lot more that I disliked. Following is a brief discussion of both.

Things I will miss about Houston/Texas

Food/”Shef”/Diversity

Houston has been ranked as the fourth most diverse city in the United States. According to some data that I’ve seen, there are more Pakistanis living in Houston metro area than anywhere else in the US. A lot of Vietnamese refugees during the 1970s settled there and the Hispanic community has always had a foothold in the city. I remember once interacting with people from nine nationalities in a single day while I was at MD Anderson. As with other diverse places, I didn’t find many regional/national ghettos in the metro area. However, there are places with more people of one ethnicity than another; with an abundance of Desis in Sugarland, same in the Chinatown area but you can find different ethnicities almost everywhere in the city.

Mahatma Gandhi district/Hillcroft Avenue offers some of the best Indian/Pakistani restaurants in the country. I will certainly miss the Halwa puri, chaat options, and Indian vegetarian food available in the area. A year or so ago, I found out about a food service where you can order home-cooked food from local chefs, called “Shef”. I availed myself of that service every week and had some delicious food without having to cook it myself. Shef is available only in a few cities in the U.S. (NYC, San Francisco, L.A, Houston, and D.C. as far as I’ve checked) and I will sorely miss the time it saved me and the variety of Indian food that I could taste at a great cost.

There were also many “fusion” foods that chefs created because of diverse cultures. Halal southern hot chicken sandwiches and Texan-Vietnamese tacos were just two examples. 

Another example of diversity was a halal grocery store in the same shopping plaza as “battle rifle company”. 

Organized medicine 

One of my friends in Miami told me before I arrive in Houston that Texas is a great place for doctors to live and work. I did not know what she meant and didn’t press her to explain why. Many years later, I understand what she meant. It was not just about average salaries or jobs, both of which are plentiful in Texas. It has to do with tort reform in the state that was enacted in the early 2000s after long-term advocacy by Texas physicians. I had the unique opportunity to interact and work with some of the people who worked behind the scenes at the time advocating for tort reform.

I got my first taste of organized medicine through the Texas Society of Pathologists (TSP). I started off as a liaison from TSP to my program and eventually ended up being Chair of a committee and being on other committees. TSP is the oldest pathology society in the US (established 1921) and is also the most active state society in the field. TSP works under the umbrella of the Texas Medical Association (TMA). TMA has more than 55000 members including medical students, trainees, and licensed physicians. TMA was responsible for getting tort reform enacted in the state because residents were leaving the state after training in droves because of high liability insurance rates in the late 1990s and early 2000s.

TMA is a behemoth with millions of dollars in assets, lobbyists in Austin, a liability insurance trust, and a foundation that gives away millions of dollars to deserving medical students across the state. TMA also gives out educational loans to medical students and residents at very low-interest rates. I was part of the Resident-Fellow section and served on the board of the TMA foundation for a year, followed by a year of the TMA board of trustees. During my time on the board of trustees, physicians in Texas faced unprecedented challenges such as Texas laws S.B. 6 and S.B.8 and a national dispute over the “No Surprises Act” for which TMA sued the HHS.

The house of medicine is under assault from many sides. Right-wing assault on reproductive care, private equity eating up hospitals, encroachment from extender services like physician assistants and nurse practitioners (called “scope of practice”), and Medicare cuts are some of the highlights. TMA is involved in fighting all of these, on a state and national level.

Things I will NOT miss about Houston/Texas

The weather 

Before I arrived in Galveston, my professor friend from Rice had warned me about hurricanes. Galveston Island was decimated by “The Great Storm” of 1900 and the whole city had to be rebuilt. Since then, other hurricanes have affected Galveston, the most recent being “Ike” whose storm surge flooded the island, at some points reaching six feet in height. My friend’s prophecy almost came true in August 2017 with Hurricane Harvey, but instead of Galveston, it caused massive flooding in Houston. Since then, I became an amateur meteorologist between June 1st and late October (hurricane season) every year, trying to discern which tropical disturbance could affect us when. We had some near misses in the last few years until there was a snow storm in February 2021, which caused blackouts, reminding me of Pakistan.

Even besides the hurricane season, Houston’s weather was frustrating at best. On January 1st, 2022, it was 80 degrees in the afternoon, dropping to 35 degrees at midnight. Houston weather resembled Lahore weather quite a lot, with humidity as the cherry on top. It could be 80 degrees with a real feel of 103 because of humidity. Even A.Cs don’t work above a certain temperature. Last year, between July and September, our central A.C. couldn’t cool off during the last few hours of the day and we were stuck between 73 and 78 degrees until late at night. The temperature started soaring in late May and days would be hot and humid till December. And it is only getting worse with climate change. A friend recently posted on Facebook that “Texas is that feeling when you open the oven to check on your cookies and you burn your face. Only there are no cookies and you can’t shut the oven door”. Just as I was writing this, saw this headline: “Extreme heat pushes highs over 110 in Texas as power grid nears brink”.

Urban Sprawl 

Harris County, with Houston as its main city, has a larger population than more than 30 states in the U.S. Houston is second only to Dallas in terms of cars per household in the U.S. as well. Combine these two facts with the never-ending expressways and you have a city in which you have to drive at least 30 minutes to go anywhere. I remember carpooling with a guy once who drove from his house in the Northern part of Houston to Galveston (almost a two-hour journey) starting at 4:30 am. He would leave Galveston in the late afternoon to get home by 6:30 pm. This is not a typical drive in the area but many people I knew (including myself) had long commutes every day. Texas is mostly flat so all you get along your drive are strip malls and gas stations. As a result, greenhouse gases generated on Texas roads account for 0.5 percent of total worldwide carbon dioxide emissions, even as the state accounts for 0.38 percent of the world’s population. The only good thing about roads in Houston are the feeder roads, so if you miss an exit, you can take the next one and turn around.

For anyone more interested in reading about Houston’s infrastructure issues and history, Stephen Klineberg’s book “Prophetic City: Houston on the cusp of change in America” is an excellent read.

An imaginative take on Texas roadways in the Texas Observer: https://www.texasobserver.org/the-road-home/

Politics

Texas is second only to California in terms of residents. As the saying goes, everything is big in Texas. That includes the disregard that politicians have for their constituents. The late great Molly Ivins, one of my favorite Texans of all time, once wrote this about the Texas legislature: “As they say around the Texas Legislature, “If you can’t drink their whiskey, screw their women, take their money, and vote against ’em anyway, you don’t belong in office”. A friend of mine from Lahore once called and asked how Texas treated people. He was intrigued because he had read in the news that a lot of businesses were moving their HQs to Texas. I told him that if you are not a straight, white, Christian man with a small business in the state of Texas, the state government doesn’t care if you live or die.

Texas lags behind on all key indicators of education, healthcare (despite it being so good for doctors), nutrition, and income inequality compared to other big states in the union. There are more uninsured people in the state than anywhere else because Texas politicians refuse to expand Medicaid and impose work requirements on the poorest people. Maternal mortality rates are even lower than the national average. Texas’s power grid is not connected to the national grid, which makes a great advertisement for “doing it all alone” but is a terrible idea in a state so prone to natural disasters. The level of corruption in Texas has been phenomenal over the years, regardless of which party was in power (another one of my all-time favorites, LBJ was an emblem of that). Because of constant gerrymandering, one party has been permanently in power for the last two decades and will be, for the foreseeable future. Even Beto (who has his faults) couldn’t defeat one of the most hated men in the country in Texas. While moving away from a place that has different politics than yours is not always possible or beneficial, I found the political climate to be smothering.

I could live with the monster trucks with “Infowars” stickers at our local grocery stores or people I played pickleball with wearing NRA shirts or our one-time neigAbdulhbors who stopped interacting with us as soon as they saw the color of my skin but I couldn’t live with S.B. 8 (the vigilante law) or the Billboards along highways congratulating Texas with a picture of multiple babies as soon as Roe was repealed or when a bigwig in TMA boasted about hosting Greg Abbot at their house for a fundraiser.

For a good review of Texas’s political history and impending future, Lawrence Wright’s “God Save Texas: A journey into the soul of the lone star state” is highly recommended.

Will I ever go back to Texas?

I have been asked this question by friends and acquaintances many times since I decided to leave. As of now, my answer is a firm “No”. I may visit occasionally for a conference or to visit my residency program but I don’t see why I would want to live in Texas if I have the choice. My life was changed completely while I was there and I am thankful for many things that happened when I was there, friends that I made and spent time with, meals that I cherished but also, heartbreak and forgettable memories.

P.S: The astronauts originally said: Houston we have had a problem.

 

The Toda are different

A new paper on Southwest Indian genetics highlights the Toda sample from Genomes Asia. People in the comments of this weblog have asserted this small southern tribe may have the most “Indus Valley Civilization” ancestry in the subcontinent. This is perhaps an exaggeration, but, looking at the admixture plots the Toda clearly have hardly any steppe ancestry, but a lot less “ASI” ancestry than their tribal neighbors, with the balance being something like the IVC ancestry.

Genomes Asia doesn’t make it’s data public, and for ancestry purposes I don’t think they’ve done the best job.

Global 25 is good, but a minor issue

ArainGang, has posted a pretty interesting map of various ancestry components in the subcontinent by population. It’s pretty good, especially for the south and west of the subcontinent. But, there is something weird going on in the northeast: a lot of these populations have “Ancestral Indian” (Andamanese) ancestry but hardly anything else East Asian. This seems wrong. In fact, the Khasi are on a cline to Bengalis. I ran a few analyses on samples with the Andamanese and I just don’t see that Global 25 is doing this right.

In the Global 25 model above the Khasi are 33% Ancient Indian, proxy for AASI, who are most closely related to the Andamanese. But you see in the analysis here the Khasi are along the India cline, but very shifted to the Han Chinese.

I ran a three-population test with a bunch of populations. You can see here that though the Andamanese are in the data set, the Khasi are best thought of as a mix of Han Chinese with an on-elite North Indian population.

pop apop bf3 staterrorZ-score
KhasiUP_DalitHan_N-0.00127270.000328938-3.8691
KhasiUP_Bihar_KanjarsHan_N-0.00102210.000334709-3.0537
KhasiIPHan_N-0.001201910.000481175-2.49787
KhasiSintashta_MLBAHan_N-0.000804550.000392122-2.05179

What does this mean? I don’t think it’s a big deal. If the population does not have East Asian ancestry to a great extent the plot by Araingang looks fine. But, obviously, Global 25 has some kinks that people need to consider. This is important because people often come to me with Global 25 as if it’s authoritative. It’s not. It’s just another way to reduce genetic variation in a human consumable fashion.

On being an “upper caste” “Muslim”

So I was talking to a friend, a Guju bania who visits their “family temple” now and then. This person is from a very tight-knight community. We were talking about whether I am “upper caste,” and their point was that most of my ancestors were from the bhadrolok literate elites of Bengal. It seems I’m mostly Kayastha, with a recent Bengali Brahmin in the mix, and reputed Iranian (Pathan and Persian) ancestry on both sides a very long time ago.

But, as I thought through the issue and reflected, I realized why the appellation annoyed me. There is no community of people of Muslim background who are mostly Kayastha with some Brahmin and ashraf ancestry. Yes, there are Muslim cates groups, like Ismailis who are clearly from banias or literally Muslim Kayasths (though most now intermarry with other Muslims). But that’s not me or my family; we are from a well-off background, but our identity is that of generic Bengali Muslims. Our origins are upper caste, but caste is irrelevant to our social reality (class though, is).

This is worth a post because I think this is going to be the case with later generations of Indian Americans. Because of the class and caste backgrounds, Indian Americans descend from ancestors will tend to be upper caste and upper-middle class. But their identity will be a new one, unrelated to the solidities of the Indian subcontinent. In this way, Indian Americans may have upper-caste privilege, but caste as a social institution just doesn’t function as it does in the subcontinent. The privilege is carryover, not operational.

So when a lot of Lefty commentators accused me of defending upper caste people because I’m an “upper-caste Muslim” I didn’t even know what to say. That’s just not part of my identity, or that of my family, though in a heritage sense that’s true. In the near future young Indian Americans who are half-Khatri and 1/4th Iyer and 1/4th Reddy would be verbally abused as “upper caste” and be just as confused as to what that even means.

Brown Pundits