The Genetics of Obvious Traits 

 

A considerable fraction of medicine can be practiced without instruments and a considerable fraction of human interest (and well-being) resides in ‘obvious’ traits. Most of these are common, multigenic traits that are considered normal, non-disease, sub-clinical. They are seen as less stigmatizing and less ‘private’, because they can be seen without DNA tests and the alleles are all roughly equally ‘healthy’ (in contrast to cancer, heart, psychiatric diseases which are generally less obvious, and riskier if disclosed).  Nevertheless, obvious traits can greatly impact Quality Adjusted Life Years (QALY) in a variety of ways, and can impact studies of common diseases (causal and/or diagnostic).  They affect our ability to sense danger, employment options, whether and with whom we associate, our choice of food, etc.   The combinations of traits and drugs that are taken might interact with one another (e.g. see Vioxx).  Most of these traits are suitable for self-reporting (e.g. height and drug doses) and hence synergistic with drastically lowered costs of genotyping.

 

These traits are often at obvious interfaces with our environments.and hence study of them helps us appreciate the nature-nuture balance. Many of these are related to ‘identifiability

’ and hence can benefit from special informed consent for research (noting that nearly all modern genetic data are ‘identifying’; see references below). We hope that $4K  ($500 in a couple of years) per subject will suffice for resequencing the most conserved 1% of each diploid genome including the most striking exons, enhancers, UCEs, miRNAs etc. PGP subjects are already consented for highly integrative omic & medical imaging studies and are highly informed, engaged, and competent for detailed self-inspection. We will try to reconsent HapMap research subjects  too. Suggestions for other traits and/or how to approach the project are welcome.

Church, GM (2005) The Personal Genome Project. Nature EMBO Molecular Systems Biology

McGuire AL, Gibbs RA (2006). Genetics. No longer de-identified. Science. 312:370-1.

Lin Z, Altman RB, Owen AB. (2006) Confidentiality in genome research. Science. 313: 441-2.

Kohane IS , Altman RB (2005) Health-information altruists - a potentially critical resource.  N Engl J Med 353: 2074-7.


Trait examples in rough order from head to foot (potential medical consequences,  therapeutic/preventative devices, nutritionals, & pharmaceuticals, if any in parentheses) [known Genetic variants in brackets]

Hair:  Whorl direction

Baldness (minoxidil) [alopecia]

Eyebrows

Eyes: Near/Far-sightedness (glasses)

Color vision [colorblindness]

Night vision (image intensifier) [night blindnesses]

Iris color [ARMD]

Retina exam

Stereo vision

Face:  [Malformation syndromes],

Wrinkles (Botox)

Lip:  [Cleft palate] (surgery)

Hirsutism (calcium thioglycolate)

Ears: Pitch,

Sensitivity (hearing aids)

Nose: Size (breathing disorders),

Olfactory variation

Mouth: breath, throat exams,

polymorphic chemical sensitivities e.g. PTC taste [TAS2R38]

voice

exhaled aerosols (airborne pathogens)

Skin:  Body odor, Perspiration, Pheromones,

Surface texture (psoriasis),

Immune components (acne treatments) [acne]

Skin color (impact on vitamin D & sunburn)

Hands: Dermatoglyphics (&syndromes)

Handedness

Arthritis   (corticosteroids)

Internal sensors: Proprioceptor, Repetitive stress syndrome

Back:  Strain sensitivity  [IDD] (analgesics)

Feet:  Plantar fasciitis  (orthotic shoes)

Athlete’s foot  (miconazole, itraconazole, terbinafine, keratolytic salicylate)

Some ‘Obvious traits’ include more integrated body measures

Height  (hGH [short stature]) [tall Marfan]

Weight (phenethylamine [obese])  [anorexia]

Metabolic polymorphisms (vitamins, minerals, insulin)

Pulse

Sleep & Circadian variation    (caffeine, amphetamines, modafinil)

Motion sickness  (Dramamine, and Scopolamine)

Dyslexia  (training)

Attention-ADHD  (Ritalin)

Depression (Prozac)

Allergies (antihistamines, cortisone, epinephrine, theophylline)

Headache (analgesics)

Less obvious & less medical traits. Some traits while considered ‘obvious’ to some, are complex enough combinations the above traits and the medical consequences small or indirect enough that they probably do not merit immediate inclusion in the above list, e.g. athletics, social behavior, intelligence, success, and beauty

-- GMC 20-Sep-2006 updated 23-Sep