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, sexual variations, neurological/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 are interested in discussions about the suitability of reconsenting subjects in existing studies such as HapMap, Health Professional's study, Nurses Health Study I & II, Washington County study, Womens Health study, Women's Health Initiative, NCI PLCO study, Am Cancer Soc CPS II-Lifelink study, Multiethnic Cohort study, VITAL cohort, Agricultural Health study, Southern Community Cohort study, Black Women's cohort study, Iceland DeCode, UK Biobank, Vanderbilt, etc. (see HSPH Pooling Project. Suggestions for traits to add or subtract, other studies or other aspects of 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 -- including links for medical consequences, (therapeutic/preventative devices, nutritionals, & pharmaceuticals, if any in parentheses) [known genetic variants in brackets]
Hair: Whorl direction
Baldness (minoxidil) [alopecia]
Eyes: Near /Far-sightedness (glasses)
Color vision [colorblindness]
Night vision (image intensifier) [ night blindnesses]
Iris Color [ARMD]
Retina exam
Stereo vision
Face: [Malformation syndromes]
Brain: Headache (analgesics)
Sleep & Circadian variation (caffeine, amphetamines, modafinil)
Motion sickness (Dramamine, and Scopolamine)
Dyslexia (training) , Attention-[ADHD] (Ritalin) , Depression (Prozac)
Wrinkles (Botox)
Lip: [Cleft palate] (surgery)
Hirsutism (calcium thioglycolate)
Ears: [Pitch]
Sensitivity (hearing aids)
Nose: Shape -- breathing disorders (CPAP), Olfactory variation
Mouth: breath, throat exams,
Polymorphic chemical sensitivities e.g. PTC taste [TAS2R38]
Digestion [reflux, gas,ulcer] (antibiotics, antacids, PPIs)
Voice Exhaled aerosols (airborne pathogens)
Skin: Body odor, Perspiration, Pheromones,
Surface texture [psoriasis] (topicals, photo-treatments) ),
Immune components (skin treatments) [acne]
Skin color (impact on vitamin D & sunburn)
Hands: Dermatoglyphics (&syndromes)
Arthritis (corticosteroids)
Internal sensors: Proprioceptor, 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 (Orlistat, Phentermine, Sibutramine) [obesity] [anorexia]
Metabolic polymorphisms (vitamins, minerals, insulin)
Allergies (antihistamines, cortisone, epinephrine, theophylline)

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 would not be in the above list, e.g. athletics, social behavior, intelligence, success, and beauty, but do merit continued ethical, legal and social implications (ELSI) discussion.

--GMC 20-Sep-2006 updated 5-Jan-2007