APOE - Revision history

Bradley Monk at 07:12, 10 March 2021

2021-03-10T07:12:16Z

← Older revision		Revision as of 00:12, 10 March 2021
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	The ''rs429358'' SNP is located in the fourth exon of the ApoE gene (~~[https://goo.gl/Ufsm1y~~ 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''rs7412'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.		The ''rs429358'' SNP is located in the fourth exon of the ApoE gene (19:45411941)<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''[https://goo.gl/Ufsm1y rs7412]'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.

Bradley Monk at 20:36, 11 November 2018

2018-11-11T20:36:22Z

← Older revision		Revision as of 13:36, 11 November 2018
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	== SNPedia INFO ==		== SNPedia INFO ==
	----		----
			https://www.snpedia.com/index.php/APOE

	The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.		The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.

Bradley Monk at 09:35, 9 January 2018

2018-01-09T09:35:33Z

← Older revision		Revision as of 02:35, 9 January 2018
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	rs7412 19 45412079 44908822 C T missense		rs7412 19 45412079 44908822 C T missense

	The ''rs429358'' SNP is located in the fourth exon of the ApoE gene ([https://goo.gl/Ufsm1y 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''rs7412'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.

	* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs429358 rs429358]		* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs429358 rs429358]
	* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs7412 rs7412]		* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs7412 rs7412]


			The ''rs429358'' SNP is located in the fourth exon of the ApoE gene ([https://goo.gl/Ufsm1y 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''rs7412'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.

Bradley Monk at 09:34, 9 January 2018

2018-01-09T09:34:46Z

← Older revision		Revision as of 02:34, 9 January 2018
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	rs7412 19 45412079 44908822 C T missense		rs7412 19 45412079 44908822 C T missense

	:: [https://~~www.ncbi.nlm.nih~~.~~gov~~/~~projects/SNP/snp_ref.cgi?rs=rs429358 rs429358~~] &		The ''rs429358'' SNP is located in the fourth exon of the ApoE gene ([https://goo.gl/Ufsm1y 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''rs7412'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.
	~~[https://www.ncbi.nlm.nih~~.~~gov~~/~~projects/SNP/snp_ref~~.~~cgi?rs=~~rs7412 rs7412]

	~~The ''rs429358'' SNP is located in the fourth exon of the ApoE gene (~~[https://~~goo~~.gl/~~Ufsm1y 19~~:~~45411941])<sup>(note this position is for reference genome GRCh37~~.~~p13)<~~/~~sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''~~. ~~If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''~~rs7412~~'' loci harbors the common allele (''~~rs7412~~-(C)-ref''), the combination is known as '''APOE-ε4'''.~~		* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs429358 rs429358]
			* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs7412 rs7412]

Bradley Monk at 09:33, 9 January 2018

2018-01-09T09:33:26Z

← Older revision		Revision as of 02:33, 9 January 2018
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	ApoE status is defined by these two SNPs:		ApoE status is defined by a person's combination of these two SNPs:
	* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs429358 rs429358]
	* [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs7412 rs7412]

	'''rs429358''' is located in the fourth exon of the ApoE gene ([https://goo.gl/Ufsm1y 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is '''rs429358(T)(ref)'''. If this allele is '''rs429358(C)(alt)''' and the same chromosome also harbors '''rs7412(C)(ref)''' allele, the combination is known as an APOE-ε4 allele.


	SNP CHR POS(GRCh37) POS(GRCh38) REF ALT MUT		SNP CHR POS(GRCh37) POS(GRCh38) REF ALT MUT
	rs429358 19 45411941 44908684 T C missense		rs429358 19 45411941 44908684 T C missense
	rs7412 19 45412079 44908822 C T missense		rs7412 19 45412079 44908822 C T missense

			:: [https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs429358 rs429358] &
			[https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs7412 rs7412]

			The ''rs429358'' SNP is located in the fourth exon of the ApoE gene ([https://goo.gl/Ufsm1y 19:45411941])<sup>(note this position is for reference genome GRCh37.p13)</sup>, affects the amino acid at position 130 of the resulting protein; the more common allele is ''rs429358-(T)-ref''. If however ('''''1''''') this loci has the alternate allele (''rs429358-(C)-alt'') and ('''''2''''') nearby on the same chromosome the ''rs7412'' loci harbors the common allele (''rs7412-(C)-ref''), the combination is known as '''APOE-ε4'''.



	Various combinations of SNPs that constitute APOE alleles: ε2 ε3 ε4		Various combinations of SNPs that constitute APOE alleles: ε2 ε3 ε4

Bradley Monk at 09:18, 9 January 2018

2018-01-09T09:18:48Z

← Older revision		Revision as of 02:18, 9 January 2018
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	APOE 4/4 45411941 ( C , C ) 45412079 ( C , C )		APOE 4/4 45411941 ( C , C ) 45412079 ( C , C )








			== TABLES ==
			----

	{\| class="wikitable" width=100% border=1 cellspacing=5px cellpadding=30px style="background:white;color:firebrick;border: 1px solid gray;"		{\| class="wikitable" width=100% border=1 cellspacing=5px cellpadding=30px style="background:white;color:firebrick;border: 1px solid gray;"
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	\| 45411941 \|\| C \|\| C \|\| 45412079 \|\| C \|\| C		\| 45411941 \|\| C \|\| C \|\| 45412079 \|\| C \|\| C
	\|}		\|}





	~~== GENOMIC LOCATIONS ==~~
	~~----~~

	{\| class="wikitable"		{\| class="wikitable"
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	== SNPedia INFO ==		== SNPedia INFO ==
	----		----

	One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.


	The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.		The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.
Line 176:		Line 175:

	Allele specific genosets gs189 and gs188 were previously used, but have now been replaced by the genotype specific ones shown above.		Allele specific genosets gs189 and gs188 were previously used, but have now been replaced by the genotype specific ones shown above.

			One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.

	<strong>Word of caution</strong> to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets defined by the genotypes listed above (and therefore assigned by Promethease) will be inaccurate if they are based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).		<strong>Word of caution</strong> to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets defined by the genotypes listed above (and therefore assigned by Promethease) will be inaccurate if they are based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).

Bradley Monk at 09:14, 9 January 2018

2018-01-09T09:14:42Z

← Older revision		Revision as of 02:14, 9 January 2018
Line 129:		Line 129:


	== ~~DETAILED APOE~~ ==		== SNPedia INFO ==
			----

	One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.		One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.


	The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having [[heart disease]] and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having [[Alzheimer's disease]] and other diseases.		The apolipoprotein E (ApoE) gene makes a protein which, when combined with fat, becomes a lipoprotein. The lipoprotein ApoE is a very low-density lipoprotein, responsible in part for removing cholesterol from the bloodstream. Variations in ApoE affect cholesterol metabolism, which in turn alter your chances of having heart disease and in particular a heart attack or a stroke. Variations in ApoE are also associated with altered odds of having Alzheimer's disease and other diseases.

	There are three relatively common allelic variants of ApoE, as defined by two SNPs, [[rs429358]] and [[rs7412]] known as ApoE-ε2, ApoE-ε3, and [[ApoE-ε4]]. The proteins produced by these genes are called ApoE2, ApoE3, and [[ApoE4]]. The most common variant overall is the "standard" ApoE-ε3, and therefore more people inherited one ApoE-ε3 from each parent than any other of the possible pairs of variants. Note that each of these types can actually have additional changes too, so there are different subtypes as well.		There are three relatively common allelic variants of ApoE, as defined by two SNPs, rs429358 and rs7412 known as ApoE-ε2, ApoE-ε3, and ApoE-ε4. The proteins produced by these genes are called ApoE2, ApoE3, and ApoE4. The most common variant overall is the "standard" ApoE-ε3, and therefore more people inherited one ApoE-ε3 from each parent than any other of the possible pairs of variants. Note that each of these types can actually have additional changes too, so there are different subtypes as well.


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	*Apo-ε1/ε1 [[gs267~~]] [[~~rs429358]](C;C) [[rs7412]](T;T) the rare '''missing allele'''		*Apo-ε1/ε1 gs267 rs429358(C;C) rs7412(T;T) the rare '''missing allele'''
	*Apo-ε1/ε2 [[gs271]] (C;T) (T;T)		*Apo-ε1/ε2 gs271 (C;T) (T;T)
	*Apo-ε1/ε3 [[gs270]] (C;T) (C;T) ambiguous with ε2/ε4		*Apo-ε1/ε3 gs270 (C;T) (C;T) ambiguous with ε2/ε4
	*Apo-ε1/ε4 [[gs272]] (C;C) (C;T)		*Apo-ε1/ε4 gs272 (C;C) (C;T)
	*Apo-ε2/ε2 [[gs268]] (T;T) (T;T)		*Apo-ε2/ε2 gs268 (T;T) (T;T)
	*Apo-ε2/ε3 [[gs269]] (T;T) (C;T)		*Apo-ε2/ε3 gs269 (T;T) (C;T)
	*Apo-ε2/ε4 [[gs270]] (C;T) (C;T) ambiguous with ε1/ε3		*Apo-ε2/ε4 gs270 (C;T) (C;T) ambiguous with ε1/ε3
	*Apo-ε3/ε3 [[gs246]] (T;T) (C;C) the most common		*Apo-ε3/ε3 gs246 (T;T) (C;C) the most common
	*Apo-ε3/ε4 [[gs141]] (C;T) (C;C)		*Apo-ε3/ε4 gs141 (C;T) (C;C)
	*Apo-ε4/ε4 [[gs216]] (C;C) (C;C) ~11x increased Alzheimer's risk		*Apo-ε4/ε4 gs216 (C;C) (C;C) ~11x increased Alzheimer's risk
	<br>		<br>

	Allele specific genosets [[gs189]] and [[gs188]] were previously used, but have now been replaced by the genotype specific ones shown above.		Allele specific genosets gs189 and gs188 were previously used, but have now been replaced by the genotype specific ones shown above.

	<strong>Word of caution</strong> to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets defined by the genotypes listed above (and therefore assigned by Promethease) will be inaccurate if they are based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).		<strong>Word of caution</strong> to those with data from Ancestry.com: in our experience, based on data in OpenSNP and from Promethease users since 2006, Ancestry data always reports rs429358 as (T;T), even for people who's data from other sources indicates they are (C;T). Therefore, until Ancestry corrects this false negative problem, be aware that the ApoE genosets defined by the genotypes listed above (and therefore assigned by Promethease) will be inaccurate if they are based on (inaccurate) Ancestry data. Specifically, some percentage of Ancestry users who are supposedly gs246 positive (Apo-ε3/ε3) are actually either gs141 (Apo-ε3/ε4) or gs216 (Apo-ε4/ε4).


	Note: Although [[ApoE]] status is technically defined by these two SNPs, [[rs429358]] and [[rs7412]], a SNP in the adjacent ApoC1 gene, [[rs4420638]], is co-inherited with ApoE and thus predictive of it, as published in the following report:		Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus predictive of it, as published in the following report:

	*[PMID 17192785] The researchers found that on testing DNA samples from 1,086 well-characterized [[Alzheimer's disease]] cases, a single SNP ([[rs4420638]]) lying 14 kb distal to the [[ApoE]] locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two [[ApoE-ε4]] copies (i.e. presumably indicated by having either the [[rs4420638(G;G)]] or [[rs429358(C;C)]] genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers.		*[PMID 17192785] The researchers found that on testing DNA samples from 1,086 well-characterized Alzheimer's disease cases, a single SNP (rs4420638) lying 14 kb distal to the ApoE locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C) genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers.


	[[APOE-ε4]] carriers may have their risk of developing [[Alzheimer's disease]] modified by SNPs elsewhere in their genomes. For example:		APOE-ε4 carriers may have their risk of developing Alzheimer's disease modified by SNPs elsewhere in their genomes. For example:

	*[[rs2373115]], a SNP in the [[GAB2]] gene		*rs2373115, a SNP in the GAB2 gene
	*Inheritance of the [[rs1799724]](T) allele appears to synergistically increase the risk of Alzheimer's in ApoE-ε4 carriers and is associated with altered CSF Abeta42 levels [PMID 15895461]		*Inheritance of the rs1799724(T) allele appears to synergistically increase the risk of Alzheimer's in ApoE-ε4 carriers and is associated with altered CSF Abeta42 levels [PMID 15895461]
	*A haplotype of 3 SNPs in the [[POLD1]] gene; the combined presence of this [[POLD1]] I-G-T haplotype and the [[ApoE-ε4]] allele almost doubles the risk of AD (odds ratio: 10.09, CI: 3.88-26.25, =<0.0001) compared to [[ApoE-ε4]] carriers alone.[PMID 17498878]		*A haplotype of 3 SNPs in the POLD1 gene; the combined presence of this POLD1 I-G-T haplotype and the ApoE-ε4 allele almost doubles the risk of AD (odds ratio: 10.09, CI: 3.88-26.25, =<0.0001) compared to ApoE-ε4 carriers alone.[PMID 17498878]

Bradley Monk at 09:12, 9 January 2018

2018-01-09T09:12:35Z

@@ Line 84: / Line 84: @@
 |}
@@ Line 111: / Line 104: @@
 </syntaxhighlight>
-== APOE on GNOMAD ==
+== ADDITIONAL RESOURCES  ==
 ----
-For convenience, I've pulled the relevant AD-related APOE loci (along with several nearby flanking positions) from GNOMAD and pasted them into a datatable here:
+==== [http://www.snpedia.com/index.php/APOE SNPedia] ====
   [https://drive.google.com/file/d/1IBFQQQVbcG2GM9b5AnmmzlqPsMMDZ2GL/view?usp=sharing view csv datatable].

Bradley Monk at 08:52, 9 January 2018

2018-01-09T08:52:04Z

← Older revision		Revision as of 01:52, 9 January 2018
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	== ~~MORE DETAILS~~ ==		== STATS AND MISC ==
	----		----

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	</syntaxhighlight>		</syntaxhighlight>

	=== APOE on GNOMAD ===

			== APOE on GNOMAD ==
			----

	Get more info about APOE variants on the [http://gnomad.broadinstitute.org/gene/ENSG00000130203 GNOMAD database] provided by a great team of genomics scientists at Broad institute.		Get more info about APOE variants on the [http://gnomad.broadinstitute.org/gene/ENSG00000130203 GNOMAD database] provided by a great team of genomics scientists at Broad institute.

Bradley Monk at 08:50, 9 January 2018

2018-01-09T08:50:49Z

← Older revision		Revision as of 01:50, 9 January 2018
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	For convenience, I've pulled the relevant AD-related APOE loci (along with several nearby flanking positions) from GNOMAD and pasted them into a datatable here:		For convenience, I've pulled the relevant AD-related APOE loci (along with several nearby flanking positions) from GNOMAD and pasted them into a datatable here:
	[https://drive.google.com/file/d/1IBFQQQVbcG2GM9b5AnmmzlqPsMMDZ2GL/view?usp=sharing view csv datatable].		[https://drive.google.com/file/d/1IBFQQQVbcG2GM9b5AnmmzlqPsMMDZ2GL/view?usp=sharing view csv datatable].



	~~== REFERENCES ==~~