Angela
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See:
http://science.sciencemag.org/content/351/6274/737
This is yet another paper that explores the impact of Neanderthal introgression on disease risk. It confirms the association with What is really new and useful for the general reader is that they provide the specific snps involved, meaning we can look them up, at 23andme, for example, if we've been tested there.
"Neandertal SNPs explained a significant [likelihood ratio test; false discovery rate (FDR) < 0.05 over all phenotype tests] percent of the risk in three traits in the E1 discovery cohort (Table 1): depression (2.03%, P = 0.0036), myocardial infarction (1.39%, P = 0.0026), and corns and callosities (1.26%, P = 0.01). Neandertal SNPs also explained a nominally significant (P < 0.1) percent of risk for nine additional traits, including actinic and seborrheic keratosis, coronary atherosclerosis, and obesity."
One of the nine not mentioned in this quote is rheumatolgical disorders including rhematoid arthritis. No wonder poor Otzi had arterio-schlerosis.
"We also tested whether the percent of phenotypic variance explained by Neandertal SNPs remained significant in the context of non-Neandertal SNPs by including an additional genetic relationship matrix (GRM) computed from non-Neandertal SNPs across the rest of the human genome in the mixed linear model (11). Depression (P = 0.031), mood disorders (P = 0.029), and actinic keratosis (P = 0.036) were replicated with these stricter criteria in the independent E2 cohort."
By mood disorders they mean bi-polar disorder.
I found this interesting as well:
"Depression risk in modern human populations is influenced by sunlight exposure (18), which differs between high and low latitudes, and we found enrichment of circadian clock genes near the Neandertal alleles that contribute most to this association."
Anyway, as to the specific snps involved:
"The strongest signal was a Neandertal SNP (rs3917862, 6.5% European (EUR) 1KG frequency) in an intro"n of P-selectin (SELP) that was significantly associated with hypercoagulable state in both E1 and E2."
Clearly, the blood coagulating quickly means you're less likely to die from a wound. There are other consequences that aren't so great.
"The second replicating association was a SNP (rs12049593, 5.0% EUR frequency) in an intron of SLC35F3, a putative thiamine transporter, which associates with protein-calorie malnutrition. Thiamine is crucial to carbohydrate metabolism for all cells, particularly those with increased energy requirements (23). Decreased expression of this transporter in the brain or GI tract could exacerbate malnutrition or its symptoms. It is possible that new dietary pressures may have caused changes in carbohydrate metabolism to be beneficial in early human migrants out of Africa; indeed, there is evidence suggesting that Neandertal introgression probably influenced lipid catabolism in Europeans (9). More recently, the reduction of thiamine present in foods from the grain-refining process, as well as an increased intake of simple carbohydrates, make this a potentially harmful allele, because it could reduce thiamine availability although modern diets increase demand."
That one I don't quite understand.
"Another Neandertal SNP (rs11030043, 9.0% EUR frequency) is upstream of stromal interaction molecule 1 (STIM1) and is associated with a phenotype encompassing incontinence, bladder pain, and urinary tract disorders,"
"The last replicated association was between rs901033 (0.5% EUR frequency) and tobacco use disorder. This SNP is in an intron of SLC6A11, a solute carrier family neurotransmitter transporter that is responsible for reuptake of the neurotransmitter γ-aminobutyric acid (GABA). Nicotine addiction disrupts GABAergic signaling in the brain and reduces expression of SLC6A11 (25). This is the second Neandertal SNP to be associated with smoking risk (5). The last replicated association was between rs901033 (0.5% EUR frequency) and tobacco use disorder. This SNP is in an intron of SLC6A11, a solute carrier family neurotransmitter transporter that is responsible for reuptake of the neurotransmitter γ-aminobutyric acid (GABA). Nicotine addiction disrupts GABAergic signaling in the brain and reduces expression of SLC6A11 (25). This is the second Neandertal SNP to be associated with smoking risk (5)."
Rheumatoid Arthritis and other related polyarthritis conditions. Rs12639456
http://science.sciencemag.org/content/351/6274/737
This is yet another paper that explores the impact of Neanderthal introgression on disease risk. It confirms the association with What is really new and useful for the general reader is that they provide the specific snps involved, meaning we can look them up, at 23andme, for example, if we've been tested there.
"Neandertal SNPs explained a significant [likelihood ratio test; false discovery rate (FDR) < 0.05 over all phenotype tests] percent of the risk in three traits in the E1 discovery cohort (Table 1): depression (2.03%, P = 0.0036), myocardial infarction (1.39%, P = 0.0026), and corns and callosities (1.26%, P = 0.01). Neandertal SNPs also explained a nominally significant (P < 0.1) percent of risk for nine additional traits, including actinic and seborrheic keratosis, coronary atherosclerosis, and obesity."
One of the nine not mentioned in this quote is rheumatolgical disorders including rhematoid arthritis. No wonder poor Otzi had arterio-schlerosis.
"We also tested whether the percent of phenotypic variance explained by Neandertal SNPs remained significant in the context of non-Neandertal SNPs by including an additional genetic relationship matrix (GRM) computed from non-Neandertal SNPs across the rest of the human genome in the mixed linear model (11). Depression (P = 0.031), mood disorders (P = 0.029), and actinic keratosis (P = 0.036) were replicated with these stricter criteria in the independent E2 cohort."
By mood disorders they mean bi-polar disorder.
I found this interesting as well:
"Depression risk in modern human populations is influenced by sunlight exposure (18), which differs between high and low latitudes, and we found enrichment of circadian clock genes near the Neandertal alleles that contribute most to this association."
Anyway, as to the specific snps involved:
"The strongest signal was a Neandertal SNP (rs3917862, 6.5% European (EUR) 1KG frequency) in an intro"n of P-selectin (SELP) that was significantly associated with hypercoagulable state in both E1 and E2."
Clearly, the blood coagulating quickly means you're less likely to die from a wound. There are other consequences that aren't so great.
"The second replicating association was a SNP (rs12049593, 5.0% EUR frequency) in an intron of SLC35F3, a putative thiamine transporter, which associates with protein-calorie malnutrition. Thiamine is crucial to carbohydrate metabolism for all cells, particularly those with increased energy requirements (23). Decreased expression of this transporter in the brain or GI tract could exacerbate malnutrition or its symptoms. It is possible that new dietary pressures may have caused changes in carbohydrate metabolism to be beneficial in early human migrants out of Africa; indeed, there is evidence suggesting that Neandertal introgression probably influenced lipid catabolism in Europeans (9). More recently, the reduction of thiamine present in foods from the grain-refining process, as well as an increased intake of simple carbohydrates, make this a potentially harmful allele, because it could reduce thiamine availability although modern diets increase demand."
That one I don't quite understand.
"Another Neandertal SNP (rs11030043, 9.0% EUR frequency) is upstream of stromal interaction molecule 1 (STIM1) and is associated with a phenotype encompassing incontinence, bladder pain, and urinary tract disorders,"
"The last replicated association was between rs901033 (0.5% EUR frequency) and tobacco use disorder. This SNP is in an intron of SLC6A11, a solute carrier family neurotransmitter transporter that is responsible for reuptake of the neurotransmitter γ-aminobutyric acid (GABA). Nicotine addiction disrupts GABAergic signaling in the brain and reduces expression of SLC6A11 (25). This is the second Neandertal SNP to be associated with smoking risk (5). The last replicated association was between rs901033 (0.5% EUR frequency) and tobacco use disorder. This SNP is in an intron of SLC6A11, a solute carrier family neurotransmitter transporter that is responsible for reuptake of the neurotransmitter γ-aminobutyric acid (GABA). Nicotine addiction disrupts GABAergic signaling in the brain and reduces expression of SLC6A11 (25). This is the second Neandertal SNP to be associated with smoking risk (5)."
Rheumatoid Arthritis and other related polyarthritis conditions. Rs12639456