Ancestral Genomics: African American Health in The Age of Precision Medicine

I have developed a strong interest in Population Genetics and Evolutionary Genomics. I have grown to have the view of race as a social construct that has no biological basis. I am also looking into Scientific Racism.  I got a kindle version of the book 'Ancestral Genomics: African American Health in the Age of Precision Medicine' by Constance B. Hilliard. 

according to Amazon.com

A leading evolutionary historian offers a radical solution to racial health disparities in the United States.

Constance B. Hilliard was living in Japan when she began experiencing joint pain. Her doctor diagnosed osteoarthritis―a common ailment for someone her age. But her bloodwork showed something else: Hilliard, who had never had kidney problems, appeared to be suffering from renal failure. When she returned to Texas, however, a new round of tests showed that her kidneys were healthy. Unlike the Japanese doctor, her American primary care provider had checked a box on her lab report for “African American.” As a scholar of scientific racism, Hilliard was perplexed. Why should race, which experts agree has no biological basis, matter for getting accurate test results?

Ancestral Genomics is the result of Hilliard’s decade-long quest to solve this puzzle. In a masterful synthesis of evolutionary history, population genetics, and public health research, she addresses the usefulness of race as a heuristic in genomic medicine. Built from European genetic data, the Human Genome Project and other databases have proven inadequate for identifying disease-causing gene variants in patients of African descent. Such databases, Hilliard argues, overlook crucial information about the environments to which their ancestors’ bodies adapted prior to the transatlantic slave trade. Hilliard shows how, by analyzing “ecological niche populations,” a classification model that combines family and ecological histories with genetic information, our increasingly advanced genomic technologies, including personalized medicine, can serve African Americans and other people of color, while avoiding racial essentialism.

https://www.amazon.com/Ancestral-Genomics-American-Precision-Medicine/dp/0674268601/

Race and Genetics: Perspectives of Precision Medicine 2023

according to her book and her presentations that are available on youtube

Race and Genetics: Perspectives of Precision Medicine 2023

https://www.youtube.com/watch?v=XLg0zSQfEAE

Talking Data Equity with Dr. Constance Hilliard

https://www.youtube.com/watch?v=t46lI2rmhR0

Precision Nutrition at the Intersection of History and Genomics

https://www.youtube.com/watch?v=gxHdXoresHg&t=1038s

It's not the race of patients that doctors should be taken into account. It's their specific ancestry. Health disparities among "racial" groups in American may be explained in large part by inexact dietary guidelines. Medicine should focus on ecological niche populations instead of dividing patients into groups based on race.

There are approximately 22,000 genes. The actual number of gene variants is 335 million, and they do not correspond to our racial classifications. Some are neutral. Some trigger diseases. Many others create adaptations that allow humans in different ecological environments to function and to survive. Our human diseases are population specific. The groups that share the same disease triggers will be highly specific and highly localized. 

African populations carry the largest amounts of genetic diversity even though they share similar outward traits. The scientific community now concurs that the San and Rainforest Hunter-Gatherer (RHG) groups carry the greatest amount of genetic diversity of all human populations as they are the living descendants of the oldest surviving branch of early humans. Twice as many gene variants are found in Africa as any where else on Earth. Variants found in West Eurasians associated with light colored skin,hairs,and eyes are also found in the Khoisan. Genetic evidence now shows that many “racial phenotypes” are in fact variants embedded in the African genome, which is parental to us all. These variants lie dormant, unexpressed, until a population’s relocation to a challenging new environment requires expression of such traits as lighter skin color and straighter hair—which offered survival benefits such as greater penetration of the sun’s ultraviolet light into the body.

Only 3 percent of the African genome has been studied or sequenced. The pattern of genetic variation is one of nested subsets, such that the variation in non-African populations is a subset of the variation found in African populations. There is an irrational belief that our species' parental genome holds fewer immunological revelations than its out-of-Africa subsets. The genomes of Africans are assumed to be replete with inconsequential and even primitive gene variants. 

Genome-wide association studies work poorly on African Americans because the databases involved are calibrated to match gene variants found in Northern Europeans for the targeted disease. European-derived Polygenic Risk Scores were poor predictors of disease susceptibility in American minorities of non-European genetic ancestry.  The predictive value of polygenic scores derived from European ancestry was only one-third as informative for African ancestry. Polygenic Index constructed from GWAS in samples of European genetic ancestries are found to have much lower predictive power in samples with other genetic ancestries. Non-Europeans are woefully underrepresented in genomic datasets. Over 95% of GWAS participants are Europeans and less than 1% of GWAS participants are of African ancestry including Africans and African Americans. 

Sickle cell anemia was often referred to as proof that inherited differences between "Blacks" and "Whites" could be translated into a cognitive hierarchy. Sickle cell anemia is a byproduct of natural immunities to malaria and is therefore found in Southern European counties and parts of India. Most East and Southern Africans do not inhabit malarial areas, lack natural immunites to those pathogens, and do not carry the sickle cell gene. 

Coastal West Africans like Europeans were genetically accustomed to consuming between 3,000 and 5,000 mg/sodium/day,  but the ancestors of African-Americans lived on 200 mg/sodium/day.  The ancestors of African Americans came from the deep interior of West Africa, and it is a region that is one of the most sodium deficient in the world. The G1 and G2 APOL1 gene variants are highly retentive of sodium. They function as natural immunity against Trypanosomiasis. They are found almost exclusively in people of interior West African ancestry.  Medical researchers have recently identified the function of these variants as being associated with high rates of hypertension and a two-to-100-fold increased of kidney disease development.  African American's Median admixture ratio is 74% West African, 24% Northern European, 1% Native American.  Current medical research simply overlooks the unique ecological conditions of African American's genetic ancestry. Millions of dollars are allocated to studies that continue to attribute this population’s salt-sensitive hypertension and kidney failure solely to stress resulting from racism.

The components of an Ecological Niche Population (ENP) model is defined by four shared comparents - the shared geographic factor, the admixture factor, the shared disease factor, and the shared disease-triggering factor. The process of applying the ENP Model begins with data from racial/ethnic health disparities research - a vibrant new field in medicine that calls attention to health differences among American demographic groups.  It is not about skin color or phenotype but about disease risks and the susceptibilities are linked to a shared genetic adaptation to a particular ancestral environment. 

My 23andme  Ancestry/Chromosome Painting (data is phased with my mothers: top chromosomes are maternal and bottom chromosomes are paternal)

44.3% West African

18.5% Southern European

17.7% Northwestern European

9.3% Ashkenazi Jewish

5.4%  Congolese/Southern East African

2.0% Broadly Northern European

1.7% Indigenous American

0.6% Northern West Asian

0.3% Chinese/Southeast Asian

0.2% Unassigned

My father's ancestry was African American with some European that consisted of mainly English and French (from the Acadians) with distant Irish, Swiss, German, Polish, and Danish. There was also Native American ancestry and Malagasy ancestry. Almost all of his 2nd great grandparents were enslaved African Americans in Southern Louisiana with the exception being his maternal European  American 2nd Great Grandfather who was the son of an English American plantation owner and a 3/4 Acadian woman.  His Y DNA haplogroup was E-BY101982 (an E2b1a branch), and his Mitochondrial DNA haplogroup was L3e1. Both are Sub Saharan African haplogroups.

My maternal grandfather's ancestry was Cape Verdean (Portuguese and Sub Saharan African), Puerto Rican (Spanish, Sub Saharan African, Taino), and Madeiran (Portuguese with some Sub Saharan African).  His mitochondrial DNA haplogroup was L0a2a2 which revealed that his maternal grandmother of Madeiran ancestry was part Sub Saharan African and not full Portuguese.

My maternal grandmother's father's ancestry was Colonial European American of mainly English with some German, Scottish, Swiss, Irish, Welsh, Dutch, and Frisian.  Y DNA haplogroup was  J-Z37545 (a J2a4h haplogroup) which is a European haplogroup.

My maternal grandmother's mother's ancestry was Ashkenazi Jewish American with a father born in Romania which is located in the Balkan region in Southeastern Europe and a mother born in Courland in the area in the Russian Empire that became Latvia which is located in the Baltic region in Northeastern Europe. Her Mitochondrial DNA haplogroup was J1c14 which is a European haplogroup.

I have the G1 APOL1 variant 

22-36265995-AATAATT-A    

NM_003661.4(APOL1):c.1164_1169del (p.Asn388_Tyr389del) traditionally known as G1 

rs71785313

Inframe Deletion

11,305 out of 1,612,914 (0.7009%)

Highest allele frequency is in African/American at 10,174 out of 74,912 (13.58%)

Allele Registry (clinicalgenome.org)