Inbreeding

I have found out I am actually from West Virginia. Ok, I am just joking.

I knew that my family had a history of marriages among relatives. After all I have only 10 great-great-grandparents instead of the usual 16. With my genome in hand, I set about to quantify the inbreeding.

First, I used David Pike’s Homozygosity tool. It analyzes your genome to find significant runs where the same haplotype is inherited from both parents. Large portions of the human genome are like that. The length of these homozygous regions, however, varies depending on the relation of your parents. If your parents are closely related (first cousins in my case), then you will have longer runs. If your parents are distantly related, then over the generations those genes have had a chance to recombine and so you will have shorter runs that are homozygous.

Overall, the percentage of my autosomal (i.e. on chromosomes 1-22) SNPs that are homozygous is 71.767 and I have 41 runs of homozygosity (ROH) of length at least 200. Here are some of my longest runs:

  • Chr 1 has a ROH of length 6009 (30.95 Mb)
  • Chr 8 has a ROH of length 5819 (33.00 Mb)
  • Chr 9 has a ROH of length 5877 (57.81 Mb)
  • Chr 9 has a ROH of length 5941 (24.38 Mb)

Let’s look at my homozygosity percentage by chromosome.

Chr 1: 71.734 %
Chr 2: 69.952 %
Chr 3: 65.741 %
Chr 4: 71.563 %
Chr 5: 69.270 %
Chr 6: 76.025 %
Chr 7: 69.445 %
Chr 8: 72.690 %
Chr 9: 93.323 %
Chr 10: 69.765 %
Chr 11: 71.866 %
Chr 12: 68.443 %
Chr 13: 74.184 %
Chr 14: 68.571 %
Chr 15: 73.087 %
Chr 16: 66.541 %
Chr 17: 77.555 %
Chr 18: 67.763 %
Chr 19: 66.267 %
Chr 20: 66.228 %
Chr 21: 79.902 %
Chr 22: 69.896 %

A majority of chromosomes seem to have reasonable percentages while chromosomes 4, 6, 8, 11, 13, 15, 17 and 21 are high. However, chromosome 9 is really weird: It is 93.323% homozygous.

David Pike writes that:

So far the largest ROHs in 23andMe V2 data that I am aware of consist of:

  • 9191 consecutive tested SNPs, corresponding to a DNA segment of length 49.99 Mb.
  • 6129 consecutive tested SNPs, corresponding to a DNA segment of length 39.05 Mb.
  • 5594 consecutive tested SNPs, corresponding to a DNA segment of length 28.95 Mb.
  • 4644 consecutive tested SNPs, corresponding to a DNA segment of length 27.71 Mb.

The highest percentage for overall autosomal homozygosity that I have so far seen from 23andMe V2 data is 71.763%.

As you can see, I am an extreme case.

A number of members at DNA Forums reported their homozygous percentage. Of all those listed, mine is the 2nd highest.

According to the paper Genomic Runs of Homozygosity Record Population History and Consanguinity:

South/Central Asians and West Asians have more than three times as many ROH in all categories over 4 Mb long than sub-Saharan Africans and other Eurasians. 19% of individuals from these populations have ROH over 16 Mb in length, consistent with the high prevalence of consanguineous marriage (marriage between individuals who are second cousins or closer) in these populations.

My total ROH length (segments > 0.5Mb) is about 282Mb which is about 1.2 standard deviations above the Central/South Asian sample mean in that paper. But I am more than 1.7 standard deviations above the mean for longer segments (>5Mb).

Let’s take a look at a graph from the paper’s supplemental material which plots total ROH length versus number of homozygous segments:

My inbreeding coefficient based on the length of long (>5Mb) runs of homozygosity in my genome (fROH5) is about 0.11 while the average in the Central and South Asian sample for the HGDP dataset is 0.015 (not directly comparable due to different number of SNPs used to calculate).

Finally, I used Plink to calculate my inbreeding coefficient F using all the South Asians from my reference datasets. That coefficient comes out to be 0.1184.