Multigenic traits can have single gene variants (often rare in populations) with large impacts.
Genotype: -/- means double-null for the gene (from both mother and father). +/- means one copy ok (+) and one broken (-) is sufficient to have a positive impact. The rest require very specific sequences to see the positive effect. For example E6V means that at position 6 an "E" (Glutamate amino acid codon GAG) is mutated into a "V" (Valine codon GTG).
| Gene | Genotype | Protective, resilient or extreme effects |
Potential Negatives |
| LRP5 | G171V/+ | Extra-strong bones | Low Buoyancy |
| MSTN | -/- | Large, lean muscles, low atherosclerosis | |
| SCN9A | -/- | Pain insensitive | Unnoticed harm |
| FAAH-OUT | del/del | Pain insensitive | Unnoticed harm |
| NTRK1 | del/del | Pain insensitive, no sweat | Unnoticed harm, hyperthermia |
| HSD17B13 | +/TA(lof) | Low Chronic Liver Disease | |
| HOXA11 | unstated | Augmented manipulation ability with six-fingered hands | |
| ABCC11 | -/- | Low odor production | |
| PRNP | G127V | Prion resistance | |
| IFNL4 | dG/TT | High Hepatitis C virus clearance | |
| CCR5 | -/- | HIV resistance | W.Nile Virus & flu; bone |
| FUT2 | -/- | Norovirus resistance | Crohn's disease |
| IL23R | R381Q/+ | IBD: Crohn's disease, Ulcerative colitis | |
| HBB | E6V/+ | Malaria resistance | Exertional rhabdomyolysis |
| PKU | +/- | Ochratoxin resistance | |
| CFTR | +/- | TB or other | |
| HEXA | +/- | TB resistance | |
| APOL1 | +/- | Trypanosoma brucei | |
| APOA1 | R173C/+ | Low HDL & CVD | |
| PCSK9 | -/- | Low coronary disease | Diabetes, Low cognition |
| GHR,GH | -/- | Low cancer, stature | |
| SLC30A8 | -/+ | Low T2 Diabetes | |
| IFIH1 = MDA5 | E627X/+ | Low T1 Diabetes | |
| ANGPTL3 | -/+ | Lipid and cardiac health | |
| BDKRB2 | a/g expression | Deep Diving | |
| PDE10A | c/t incr thyroxine | Breath-hold diving | |
| EGLN1 | a/g | High altitude | |
| EPAS1 | 3.4kb del | High altitude | |
| MTHFR | A222V | High altitude | |
| EPOR | W439X | High oxygen transport | |
| BHLHE41 = DEC2 | P385R/+ | Less sleep | |
| NPSR1 | Y206H/+ | Less sleep | |
| ADRB1 | A187V | Less sleep | |
| APOE | E2/E2 | Low Alzheimer's (E2=R112C, R158C) | |
| APP | A673T/+ | Low Alzheimer's | |
| GLUK4 | del/+ | Low bipolar, high cognitive | |
| Transgenic & Knock-in mice |
| SOST | -/- | Bone loss resistance | |
| NPC1 | +/- | Ebola resistance | |
| CTNNB1 | overprod. | Radiation resistance | |
| TERT | overprod. | Low aging | |
| CDKN2A | overprod. | Low cancer | |
| TP53 | overprod. | Low cancer | |
| GRIN2B | overprod. | High learning & memory | |
| PDE4B | inhib. | Low anxiety, high problem solving | |
| FOXP2 | humanized | Learn stimulus-response associations faster | |
| CCR5 | -/- & +/- | Enhanced learning, low atherosclerosis, low hepatotox | Flavi- & Orthomyxo- viruses |
| NLGN3 | R451C/Y | Enhanced spatial learning abilities (Autism) | |
| Cognition-related gene therapies |
| NGF | overprod. | (human) Low Alzheimer's | |
| NEU1 | overprod. | (mice) Low Alzheimer's | |
| NGFR | overprod. | (mice) Low Alzheimer's | |
| miR-29b | overprod. | (human cells) Low Alzheimer's | |
| BACE1 siRNAs | overprod. | (mice) Low Alzheimer's | |
| anti-amyloid antibodies | overprod. | (mice) Low Alzheimer's | |
| APPsα | overprod. | (mice) Low Alzheimer's | |
Note: Some of the above studies need independent reproduction.
Lower case a,c,g,t are nucleotide variants (typically regulatory), while uppercase indicated amino acid variants.
See also:
Longevity:
GenAge Database of Ageing-Related Genes
Height:
~9,500 SNPs explain ~29% of phenotypic variance
Pathogens:
CFTR,NPC1,HEXA: Resistance to typhoid, cholera, mycotoxin abortions, enveloped viruses via MOGS, filoviruses, rabies via myasthenia gravis
Space:
radiation, low gravity, etc.
If you know of additional published or unpublished examples, or anyone who is exceptionally resistance to any disease, please let us know.
Bay Area Lyme Foundation
,
American Lyme Disease Foundation,
Lymedisease.org
Thanks to Jason Bobe, Cory Smith, Luke Dabin, Mark Handle, David Thompson, Noah Davidsohn, Dimitrie Leustean for suggested additions.
--GMC
26-Oct-2011 4 genes: MSTN, LRP5, PCSK9, CCR5
04-Apr-2012 5 genes: MSTN, LRP5, PCSK9, CCR5, FUT2
23-Oct-2013 6 genes: + APP
05-Feb-2014 11 genes.
10-Sep-2015 19 genes.
06-Sep-2017 28 genes.
24-Oct-2018 44 genes.
14-Aug-2019 51 genes.
09-Oct-2019 52 genes: + ADRB1
18-Oct-2019 54 genes: + NPSR1 + NTRK1
8-Nov-2019 55 genes: + APOA1