## 23andme and FDA

FDA had asked 23andme to stop its direct-to-consumer genetic testing and as a result 23andme has issued the following statement:

After discussion with officials from the Food and Drug Administration today, 23andMe will comply with the FDA’s directive and stop offering new consumers access to health-related genetic tests while the company moves forward with the agency’s regulatory review processes.

Customers who purchased kits on or after the FDA’s warning letter of November 22nd will not have access to health-related results. Those customers will have access to ancestry-related genetic information and their raw data without 23andMe’s interpretation of that data. They may receive health-related results in the future, depending on FDA marketing authorization.

Customers who purchased kits before November 22, 2013 will continue to have access to all the reports they’ve always had.

While I am disappointed at this turn of events, for our project it does not change much since 23andme will still provide raw data downloads as well as ancestry information.

## HarappaWorld HRP0375-HRP0384

Do note that the admixture components do not necessarily represent real ancestral populations. Also, the names I have chosen for the components should be thought of as mnemonics to ease discussion. I chose them based on which populations in my data these components peaked in. They do not tell anything directly about ancestral populations. The best way to look at these admixture results is by comparing individuals and populations. Finally, the standard error estimates on these results can be about 1%. Therefore, it is entirely possible that your 1% exotic admixture result is just noise.

I have also updated the group averages.

## HarappaWorld HRP0352-HRP0374

Do note that the admixture components do not necessarily represent real ancestral populations. Also, the names I have chosen for the components should be thought of as mnemonics to ease discussion. I chose them based on which populations in my data these components peaked in. They do not tell anything directly about ancestral populations. The best way to look at these admixture results is by comparing individuals and populations. Finally, the standard error estimates on these results can be about 1%. Therefore, it is entirely possible that your 1% exotic admixture result is just noise.

I have also updated the group averages.

Someone asked for the individual HarappaWorld Admixture results for the Burusho and Kalash from HGDP.

In the chart below as well as in the spreadsheet, the IDs starting with "b" belong to the Burusho and those starting with "k" belong to the Kalash individuals.

You can check the spreadsheet too.

## Personal Journey

I have had myself, my wife, my daughter, my parents, and my sister genotyped by 23andme.

From time to time, I explore my personal and family data on my other blog. If you are interested, you can read about it under the Genetics category there.

My latest post is about figuring out how my inbred genome has passed on to my daughter.

As you can see, I now have affiliate links on the sidebar. If you order a test following those links, I get a small amount for referring you.

Right now, I have FTDNA and 23andme listed there.

## HarappaWorld HRP0328-HRP0351

Do note that the admixture components do not necessarily represent real ancestral populations. Also, the names I have chosen for the components should be thought of as mnemonics to ease discussion. I chose them based on which populations in my data these components peaked in. They do not tell anything directly about ancestral populations. The best way to look at these admixture results is by comparing individuals and populations. Finally, the standard error estimates on these results can be about 1%. Therefore, it is entirely possible that your 1% exotic admixture result is just noise.

I have also updated the group averages.

Since 10 of the 24 new participants are Punjabis (with 8 being Punjabi Jatts), I now have 33 Punjabis in HAP. Therefore, I will try to write about the Punjabi samples and their results next week.

## Genetic Evidence for Recent Population Mixture in India

Finally the paper I had been waiting for ever since the conference presentations on ANI-ASI admixture dating by Moorjani et al at Reich Lab is out:

Moorjani et al., Genetic Evidence for Recent Population Mixture in India, The American Journal of Human Genetics (2013), http://dx.doi.org/10.1016/j.ajhg.2013.07.006

Here's the abstract:

Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.

In this paper, Moorjani et al calculate ANI (Ancestral North Indian) percentage as:

From Reich et al, they changed the outgroup from Papuan to Yoruba and the ANI clade group from CEU (Utahn Whites) to Georgians. I think both are much better choices. Looking at the D-statistics in Table S2, Georgians are definitely an appropriate choice for forming a clade with ANI.

Another important result from the paper is the difference in the date of admixture for Dravidians (108 generations or 3,132 years) and Indo-Europeans (72 generations = 2,088 years).

Testing for multiple waves of admixture, they find that it is more likely in upper-caste and middle-caste Indo-Europeans and the admixture history of a lot of Indian groups is more complex.

UPDATE: Razib and Dienekes comment.

## Bengalis

Let's take a look at the Bengali participants of the Harappa Ancestry Project.

I have added a suffix to the IDs where B = Brahmin, V = Vaidya and M = Muslim.

Here are the HarappaWorld Admixture results for the Bengalis which you can also see in a spreadsheet.

It's easy to see the difference between the Brahmins and others.

Razib wanted to know the origin of the East Asian ancestry among the Bengalis. So I ran a supervised ADMIXTURE with the following populations set as ancestral:

• Altaian
• Burmanese
• Buryat
• Cambodian
• Chukchi
• Dai
• Daur
• Dolgan
• Evenki
• Georgian
• Gujarati-A
• Han
• Han-NChina
• Hezhen
• Japanese
• Ket
• Kinh
• Koryak
• Lahu
• Miao
• Mongola
• Mongolian
• Naxi
• Nganassan
• Oroqen
• Selkup
• She
• Singapore-Malay
• Tibet
• Tu
• Tujia
• Tuvinian
• Xibo
• Yakut
• Yi
• Yukaghir

While most of these populations are various East Asian groups, I used the Gujarati-A as the South Asian group since it has the most South Indian + Baloch components without any East Asian influence. I used the Georgians as a proxy for West Asian ancestry.

Since it's K=36, I ran ADMIXTURE 10 times with different seeds and computed the average percentages for the Bengali participants. The number of SNPs was about 85,565. I did a similar analysis at K=35 after excluding the Tibetans, which got me 263,000 SNPs. The results were broadly similar.

I am showing only the first 12 ancestral components since all the rest were less than 0.5% for all the Bengalis (Spreadsheet).

Please do remember that in supervised ADMIXTURE, I assign the ancestral populations and the algorithm has to find the best fit using those populations. So it's not showing actual ancestry but broad affinity. Also, the exact percentages are not important and can vary when I change the parameters of the analysis. Just look at the broad trends.

The general pattern is that Bengali Brahmins have the least Eastern Eurasian and the most West Asian. The Eastern Eurasian ethnicity most closely related to Bengalis is Burmese.

Interestingly, there is a pattern of a small amount of Siberian ancestry among these Bengalis. Let's add all the Siberian and Russian Far East groups.

ID Ethnicity Siberian
HRP0244 West Bengal Rajput 5.07%
HRP0077B Bengali Brahmin 5.01%
HRP0049 Bengali 4.45%
HRP0252B Bengali Brahmin 4.01%
HRP0268B Bengali Brahmin 3.90%
HRP0023M Bengali Muslim 3.54%
HRP0316B Bengali Brahmin 3.45%
HRP0054B Bengali Brahmin 3.41%
HRP0300M Bengali Muslim 2.95%
HRP0240V Bengali Vaidya 1.78%
HRP0293B Bengali Brahmin 1.02%
HRP0291V Bengali Vaidya 0.99%
HRP0317M Bengali Muslim 0.89%
HRP0321M Bengali Muslim 0.58%
HRP0322M Bengali Muslim 0.41%
HRP0022M Bengali Muslim 0.37%
HRP0091B Bengali Brahmin 0.01%

I am not sure of the pattern here, but at least the first few are above noise thresholds.

## An Analysis of HAP by Razib

Razib Khan looked over the HarappaWorld Admixture results and posted his analysis on his GNXP blog. Go read it.