There are lots of common diseases for which the cause is not known - coronary heart disease, Alzheimer's disease, most cancers.
When a disease cause is unknown, then all kinds of weird ideas may become established as to the cause, and some of these are tenacious.
Many people imagine that myocardial infarctions (heart attacks) are caused by cholesterol, or fat - but these are not the kind of things that cause disease.
Many people imagine that 'depression' is caused by neurotransmitter abnormalities - such as low serotonin - but this is not a cause of disease, at most (if true, which it isn't) it would be a biochemical marker of disease and not a cause.
Diseases are typically quite simple and (at least since about 1900) quite common-sensical, once their causes are discovered.
Most diseases of which causes are known with confidence are caused by infections and parasites, and by various kinds of trauma - physical trauma, chemical trauma (poisoning), by accidents in development (it almost impossible to construct a human being perfectly and without defects), and by the accumulation of damage (this includes most cancers - the cancers of older age).
'Genetic' causes of disease are simply a member of the class of developmental problems - an example of how difficult (impossible) it is to build something as complex as a human without some errors.
So, for example, it is likely that the mid-twentieth century epidemic of heart disease was probably caused by some infectious agent - not known; at least, the broad facts fit those of an infectious disease, and as a basic assumption, infection is the most likely cause.
For humans, as large complex animals, invasion and colonisation by infectious parasitic agents is the basic problem in life, considering that we could not, until recently - and even now only very partially - do anything much about the way we are made, or the accumulation of damage.
As well as the damage of micro-organisms and parasites, there are problems with the body's 'immune' reactions to these invaders - and these probably cause another whole set of 'autoimmune' diseases; which may include eczema, asthma, rheumatoid arthritis and many of the other diseases that are improved by 'steroids' (glucocorticoids).
So we have the two greatest drug class discoveries in medicine in the mid-twentieth century: 1. the antibiotics, which can cure infections; and 2. steroids, which can cure pathological immune responses, i.e. pathologies in the bodies own response to infection.
What about diet?
In this broad brush approach, the most obvious factor is that humans are harmed by insufficient food: starvation is a major cause of disease throughout human history, probably the major cause in many societies with dense populations.
It seems that humans can live a full lifespan on a huge range of diets, so long as the food does not contain too much poisonous or infectious stuff.
The most striking thing about diet is how little dietary components matter to life expectancy, so long as there is enough food.
Tobacco smoke is, of course, a toxic agent - or rather, an agent including toxic properties - and the cause of most lung cancers; and also toxic are many other drugs including alcohol and prescribed drugs.
Many drugs - such as penicillin, digitalis, caffeine, opium - are indeed plant toxins evolved to poison animals who eat the plant.
Plant seeds, stems and leaves are usually poisonous to animals unless they are protected by a physical barrier (such as shell, bark, tough 'skin'); because stems and especially leaves are exposed, and the plant doesn't want its reproductive cells to be eaten. e.g. Tobacco is from leaves, caffeine from seeds, and so on.
So, there we have it. The causes of disease. If in doubt, assume one of the above.