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Snyder's major contributions to genetics and the genetic approach to medicine could be viewed through three main domains: (1) utilizing genetics to identify and treat diseases; (2) integrating concepts of genetics and heredity in scientific and medical understanding; (3) advocating for the idea of preventive genetic medicine in a bid to eliminate illnesses that result from heritable unfavorable genes. Snyder's contributions also track a shift in his academic focus from racialized aspects of population genetics in the 1920s to genetic and medical concerns more centered around the individual in the 1940s and 50s.

Blood group genetics

In the early 1920s, the debate over the ABO blood group emerged with great enthusiasm in the scientific arena. Polish bacteriologist Ludwik Hirszfeld and his wife, pediatrician Hanna Hirszfeld, proposed in 1919 that blood groups were a result of two independent genetic loci, an A gene and a separate B gene. However, in 1924, German mathematician Felix Bernstein introduced a triple-allele hypothesis, contending that population data fit better with a single blood-group gene with three alleles, A, B, O, as we know of now.

This occurred during the time when Snyder was relocating to North Carolina for his assistant professorship at North Carolina State College in Raleigh. He was two years away from his doctorate and was in the midst of choosing a dissertation topic. This problem of blood group typing appealed to him and he found that Bernstein's theory explained the discrepancies Snyder had found between the results of his own research at the time and Hirszfeld's theory. In 1925, Snyder published his thesis in the American Journal of Physical Anthropology, applying the triple-allele hypothesis to type humans based on racial groups. Collaborating with American physician William Allan, Snyder drew blood from North Carolina Cherokee Indians and quantitatively analyzed blood-group proportions among the various racial hybrids within this population. Through this, he developed a theory of classifying races based on the relative proportion of different blood groups in different populations. He characterized humans as six races: European, Hunan, Indomanchurian, Africo-Malaysian, Pacific-American, and Australian, with these races having radiated from a single human origin. It is important to note that although Snyder's work was racialized, he was mainly seeking to use science and genetics to trace the origins of human races, and never viewed the human race as composed of multiple species.

Snyder continued to apply genetics to solve medical problems, recognizing the medical impact of blood typing in not only race classification, but also blood transfusions and paternity tests. To emphasize the utility of blood typing not just in anthropology but also in medicine, Snyder expanded these ideas in his book Blood Grouping in Relation to Clinical and Legal Medicine.

Testing of heritable conditions

In the 1920s, there were only six clearly defined human traits whose genetics were well studied: the ABO blood group, the MN blood type, eye color, the direction of the whorl of hair at the back of the head, the presence of hair on the second joint of fingers and toes, and the dominant form of migraine discovered by William Allan. Snyder discovered a seventh in 1931, and developed the first genetic test for a trait.

For most people, phenylthiocarbamide (PTC) tastes really bitter, but to a significant fraction of the population, the taste is entirely undetectable. Snyder was interested in confirming whether the ability to taste PTC is a Mendelian trait and sought to understand the biological and genetic nature of this trait. In his research, Snyder collected data from 800 families with 2,843 children to cover sufficient ground on the possible genetic combinations of this allele. He found that the gene PTC is associated with acted like a classic dominant, and both alleles (the taster and non-taster ones) are common.

To test for the presence of the PTC taster allele, Snyder found a simple, cost-effective and convenient way of soaking a slip of paper in a solution containing PTC and letting the paper dry. This technique opened new ground for Snyder and other geneticists to test patients with other heritable conditions for PTC sensitivity, in hope of finding linkage groups: the presence of two genes sufficiently close to each other on a chromosome such that the inheritance of one trait indicates a high probability of inheriting the other. Snyder's findings on identifying heritable diseases was another significant contribution to the clinical applications of genetics.

Medical genetics

The reason why Snyder is the founding father of American genetics is not that much due to his numerous intellectual accolades, but his contributions to the professionalization of human and medical genetics.

During the 1930s and 40s, when Snyder was at Ohio State University, he developed and designed the first required course in medical genetics for medical students in America. He also taught this course at Duke, North Carolina and Wake Forest medical schools, and at the University of Oklahoma and to practicing physicians in Honolulu when he was at the University of Hawaii. In 1935, Snyder published his own textbook, The Principles of Heredity, which had five editions and was widely used in genetics courses. Snyder went on to establish four medical genetics programs on his own and was directly involved in the founding of at least two others. He was also a founder of the first professional society in medical genetics in 1948.

As observed recurring in his writing, Snyder advocated that doctors should learn about genetics due to six reasons: (1) genetics could aid in diagnosis; (2) it could elucidate ways to prevent people from suffering from genetic disease; (3) it could be useful when there are legal implications, such as during cases of disputed paternity; (4) it plays a role in genetic counseling for marriage and (5) pregnancy; (6) genetics is also the basis for eugenic and euthenics programs, "for the protection of society."

Eugenics

Snyder strongly believed that genetics hold great medical benefit in terms of the prevention of disease, through reducing the incidence of hereditary illness or even eliminating them altogether. He felt that "feeble-mindedness" was "probably the outstanding problem in eugenics," contending throughout the final chapter of his textbook, The Principles of Heredity, that segregation and sterilization were necessary eugenic measures to ensure that the biological inequality leading to physical and mental deficiencies were curbed.