rs7412

Chromosome : 19 , Position: 44908822

Most conditions are affected by anywhere from hundreds to millions of genetic variants (SNPs). A single SNP usually has a minor contribution to a person’s overall genetic risk for a certain condition. That is why you shouldn't consider or act on a SNP in isolation. Instead, we use SNPs to determine polygenic risk scores (PRSs), which are the basis of most health reports.

Reference Allele: C

Alternative Alleles: T

Associated Genes

APOE

CLPTM1

NECTIN2

APOC1

APOC2

APOC4

APOC4-APOC2

PPP1R37

CLASRP

BLOC1S3

NKPD1

TRAPPC6A

PVR

TOMM40

GEMIN7

MARK4

ZNF296

BCAM

RELB

BCL3

CBLC

CEACAM16

CEACAM19

KLC3

IGSF23

EXOC3L2

CEACAM20

CKM

ZNF180

ERCC2

ZNF229

POLR1G

PPP1R13L

Traits

Trait	Variant	PMID	Author (year)
Lipoprotein phospholipase A2 activity in cardiovascular disease	T	PLoS One	Yeo A (2017)
Lipoprotein(a) levels adjusted for apolipoprotein(a) isoforms	T	J Lipid Res	Mack S (2017)
Blood protein levels [BIRC2, 10046_55_3]	T	Science	Emilsson V (2018)
Blood protein levels [UBA2, 12500_88_3]	T	Science	Emilsson V (2018)
Blood protein levels [VPS29, 14318_1_3]	T	Science	Emilsson V (2018)
Blood protein levels [C5orf38, 6378_2_3]	T	Science	Emilsson V (2018)
Blood protein levels [ARL2, 12587_65_3]	T	Science	Emilsson V (2018)
Blood protein levels [CUZD1, 7943_16_3]	T	Science	Emilsson V (2018)
Blood protein levels [CEP57, 11276_1_3]	T	Science	Emilsson V (2018)
Blood protein levels [S100A13, 7223_60_3]	T	Science	Emilsson V (2018)
Blood protein levels [APOE, 2418_55_9]	T	Science	Emilsson V (2018)
Apolipoprotein B levels	T	Nat Genet	Sinnott-Armstrong N (2021)
Blood protein levels [Il16, 7672_7_3]	T	Science	Emilsson V (2018)
Blood protein levels [CRYZL1, 9207_60_3]	T	Science	Emilsson V (2018)
Blood protein levels [APOE, 2937_10_2]	T	Science	Emilsson V (2018)
Blood protein levels [PSME1, 5918_5_3]	T	Science	Emilsson V (2018)
Blood protein levels [VIMP, 11286_78_3]	T	Science	Emilsson V (2018)
Blood protein levels [HBQ1, 7965_25_3]	T	Science	Emilsson V (2018)
LDL cholesterol levels [Trans-ethnic initial]	T	Hum Mol Genet	Spracklen CN (2017)
Metabolite levels (lipoprotein measures) [Free cholesterol in large LDL]	T	Nat Commun	Kettunen J (2016)
LDL cholesterol	T	Nat Genet	Willer CJ (2013)
Low density lipoprotein cholesterol levels [Hispanic]	T	Nat Genet	Hoffmann TJ (2018)
Blood protein levels [APOB, 2797_56_2]	T	Science	Emilsson V (2018)
LDL cholesterol levels	T	Cell	Gurdasani D (2019)
Blood protein levels [FAM159B, 10635_33_3]	T	Science	Emilsson V (2018)
Blood protein levels [APOB]	T	Nat Commun	Yao C (2018)
Low density lipoprotein cholesterol levels [AA]	T	Nat Genet	Hoffmann TJ (2018)
Blood protein levels [TBCA, 12501_10_3]	T	Science	Emilsson V (2018)
Blood protein levels [GGT2, 6334_9_3]	T	Science	Emilsson V (2018)
Blood protein levels [KIN, 14643_27_3]	T	Science	Emilsson V (2018)
Low density lipoprotein cholesterol levels [EA]	T	Nat Genet	Hoffmann TJ (2018)
Lipid traits [LDL-C]	T	J Lipid Res	Wu Y (2013)
Blood protein levels [APOE, 5312_49_3]	T	Science	Emilsson V (2018)
Blood protein levels [TMCC3, 8922_4_3]	T	Science	Emilsson V (2018)
Blood protein levels [AKT2, 14685_17_3]	T	Science	Emilsson V (2018)
Blood protein levels [CTF1, 13732_79_3]	T	Science	Emilsson V (2018)
Alzheimer's disease or family history of Alzheimer's disease	T	Nat Genet	Schwartzentruber J (2021)
Blood protein levels [CKAP2, 5345_51_3]	T	Science	Emilsson V (2018)
Blood protein levels [KLRC3, 11571_75_3]	T	Science	Emilsson V (2018)
Total cholesterol levels [Hispanic]	T	Nat Genet	Hoffmann TJ (2018)
Pulse rate, automated reading	T	Unknown journal	UKB Neale v2 (2018)
Blood protein levels [APOE, 2938_55_2]	T	Science	Emilsson V (2018)
Blood protein levels [KMT2C, 11402_17_3]	T	Science	Emilsson V (2018)
Total cholesterol levels [AA]	T	Nat Genet	Hoffmann TJ (2018)
Blood protein levels [HLA-DRB3, 6962_5_3]	T	Science	Emilsson V (2018)
Blood protein levels [IFI16, 12893_159_3]	T	Science	Emilsson V (2018)
Pulse pressure	T	Nat Genet	Evangelou E (2018)
Blood protein levels [APBB2, 12753_6_3]	T	Science	Emilsson V (2018)
Total cholesterol levels [Trans-ethnic initial]	T	Hum Mol Genet	Spracklen CN (2017)
Total cholesterol levels [EA]	T	Nat Genet	Hoffmann TJ (2018)
Blood protein levels [LRP1B, 7640_29_3]	T	Science	Emilsson V (2018)
Blood protein levels [CD200R1L, 8980_19_3]	T	Science	Emilsson V (2018)
Blood protein levels [SUMF1, 6941_11_3]	T	Science	Emilsson V (2018)
Blood protein levels [TP53I11, 13022_20_3]	T	Science	Emilsson V (2018)
Medication use (HMG CoA reductase inhibitors)	T	Nat Commun	Wu Y (2019)
Blood protein levels [MAPK8, 3825_18_2]	T	Science	Emilsson V (2018)
Cholesterol, total	T	Sci Rep	Prins BP (2017)
Blood protein levels [GNAI3, 12650_43_3]	T	Science	Emilsson V (2018)
Whole body fat mass	T	Unknown journal	UKB Neale v2 (2018)
Hip circumference	T	Unknown journal	UKB Neale v2 (2018)
Mean sphered cell volume	T	Unknown journal	UKB Neale v2 (2018)
Trunk fat percentage	T	Unknown journal	UKB Neale v2 (2018)
Arm fat percentage (left)	T	Unknown journal	UKB Neale v2 (2018)
Arm fat percentage (right)	T	Unknown journal	UKB Neale v2 (2018)
Response to statins (LDL cholesterol percent change)	T	NPJ Genom Med	Oni-Orisan A (2020)
Body fat percentage	T	Unknown journal	UKB Neale v2 (2018)
HDL cholesterol levels	T	Cell	Gurdasani D (2019)
Trunk fat mass	T	Unknown journal	UKB Neale v2 (2018)
Medication use (salicylic acid and derivatives)	T	Nat Commun	Wu Y (2019)
Lipoprotein (a) levels	T	Nat Genet	Sinnott-Armstrong N (2021)
Medication use (antithrombotic agents)	T	Nat Commun	Wu Y (2019)
Medication use (agents acting on the renin-angiotensin system)	T	Nat Commun	Wu Y (2019)
HDL cholesterol	T	Nat Genet	Willer CJ (2013)
Medication use (calcium channel blockers)	T	Nat Commun	Wu Y (2019)
Lipid traits [TC]	T	J Lipid Res	Wu Y (2013)
Red cell distribution width	T	Cell	Astle WJ (2016)
Low density lipoprotein cholesterol levels	T	NPJ Genom Med	Oni-Orisan A (2020)
High light scatter reticulocyte percentage of red cells	T	Cell	Astle WJ (2016)
Immature fraction of reticulocytes	T	Cell	Astle WJ (2016)
High light scatter reticulocyte count	T	Cell	Astle WJ (2016)
Low density lipoprotein cholesterol levels (on statin treatment)	T	NPJ Genom Med	Oni-Orisan A (2020)
Red blood cell (erythrocyte) distribution width	T	Unknown journal	UKB Neale v2 (2018)
Response to statins (LDL cholesterol change)	T	NPJ Genom Med	Oni-Orisan A (2020)
Direct bilirubin levels	T	Nat Genet	Sinnott-Armstrong N (2021)
Reticulocyte fraction of red cells	T	Cell	Astle WJ (2016)
Mean spheric corpuscular volume	T	Cell	Vuckovic D (2020)
Mean reticulocyte volume	T	Cell	Vuckovic D (2020)
Lipoprotein-associated phospholipase A2 activity change in response to darapladib treatment in cardiovascular disease	T	PLoS One	Yeo A (2017)
Vitamin D levels	T	Nat Genet	Sinnott-Armstrong N (2021)
Serum 25-Hydroxyvitamin D levels	T	Nat Commun	Revez JA (2020)
Parental longevity (father's attained age)	T	Aging (Albany NY)	Pilling LC (2017)
Carotid intima media thickness	T	Nat Commun	Franceschini N (2018)
Reticulocyte count	T	Unknown journal	UKB Neale v2 (2018)
"Hyperlipidaemia, other/unspecified"	T	Unknown journal	FINNGEN_R5 (2021)
"Ischaemic heart disease, wide definition"	T	Unknown journal	FINNGEN_R5 (2021)
"Myocardial infarction, strict"	T	Unknown journal	FINNGEN_R5 (2021)
"Myocardial infarction, strict" (no controls excluded)	T	Unknown journal	FINNGEN_R5 (2021)
Alzheimer's disease (late onset)	T	Nat Genet	Sims R (2017)
Alzheimer's disease (onset at age over 80)	T	Neurobiol Aging	Lo MT (2019)
Angina pectoris	T	Unknown journal	FINNGEN_R5 (2021)
Angina pectoris (no controls excluded)	T	Unknown journal	FINNGEN_R5 (2021)
Cardiovascular disease	T	Am J Hum Genet	Kichaev G (2018)
Cardiovascular risk factors [LDL-cholesterol]	T	PLoS Genet	Smith EN (2010)
Coronary angiopasty	T	Unknown journal	FINNGEN_R5 (2021)
Coronary artery bypass grafting	T	Unknown journal	FINNGEN_R5 (2021)
Coronary artery disease	T	Circ Res	van der Harst P (2017)
Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	T	Nat Genet	Nelson CP (2017)
Coronary atherosclerosis	T	Unknown journal	FINNGEN_R5 (2021)
Coronary atherosclerosis (no controls excluded)	T	Unknown journal	FINNGEN_R5 (2021)
Coronary revascularization (ANGIO or CABG)	T	Unknown journal	FINNGEN_R5 (2021)
Coronary revascularization (ANGIO or CABG) (no controls excluded)	T	Unknown journal	FINNGEN_R5 (2021)
Disorders of lipoid metabolism	T	Unknown journal	UKB SAIGE (2018)
Disorders of lipoprotein metabolism and other lipidaemias	T	Unknown journal	FINNGEN_R5 (2021)
Emergency coronary revascularization (for ACS) (no controls excluded)	T	Unknown journal	FINNGEN_R5 (2021)
Forns index in high alcohol intake	T	Gastroenterology	Innes H (2020)
Hypercholesterolemia	T	Unknown journal	UKB SAIGE (2018)
Hyperlipidemia	T	Unknown journal	UKB SAIGE (2018)
Ideal cardiovascular health (clinical and behavioural)	T	Am Heart J	Allen NB (2016)
Ischemic heart disease	T	Unknown journal	UKB SAIGE (2018)
Ischemic heart diseases	T	Unknown journal	FINNGEN_R5 (2021)
LDL cholesterol levels in HIV infection [African American]	T	BMC Med	Chang H (2020)
LDL cholesterol levels in HIV infection [EA]	T	BMC Med	Chang H (2020)
Lipid metabolism phenotypes [L-LDL-FC]	T	Nat Genet	Kettunen J (2012)
Longevity (age >90th survival percentile)	T	Nat Commun	Deelen J (2019)
Longevity (age >99th survival percentile)	T	Nat Commun	Deelen J (2019)
Major coronary heart disease event	T	Unknown journal	FINNGEN_R5 (2021)
Mean corpuscular hemoglobin	T	Am J Hum Genet	Kichaev G (2018)
Metabolic disorders	T	Unknown journal	FINNGEN_R5 (2021)
Myocardial infarction	T	Eur Heart J	Hartiala JA (2021)
Other chronic ischemic heart disease, unspecified	T	Unknown journal	UKB SAIGE (2018)
Pure hypercholesterolaemia	T	Unknown journal	FINNGEN_R5 (2021)
Red blood cell count	T	Am J Hum Genet	Kichaev G (2018)
Response to statins (LDL cholesterol change) [baseline LDL-C]	T	Circ Cardiovasc Genet	Chasman DI (2012)
Rosuvastatin \| treatment/medication code	T	Unknown journal	UKB Neale v2 (2018)
Serum total cholesterol levels	T	Neurol Genet	Tang ME (2020)
Statin medication	T	Unknown journal	FINNGEN_R5 (2021)
Systolic blood pressure	T	Am J Hum Genet	Kichaev G (2018)
Total cholesterol levels	T	Nature	Wojcik GL (2019)

More Information

The Major "C" allele is associated with:

Alzheimer's Disease

CC = Bad version = contributes to APOE4 when combined with CC or CT genotype for rs429358.

rs429358 (C;C) + rs7412 (C;C) = APOE4/APOE4 (Bad) = 12x for late-onset Alzheimer's and 61x for early-onset disease [R].
rs429358 (C;T) + rs7412 (C;C) = APOE3/APOE4 (Bad) = >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease [R].
rs429358 (T;T) + rs7412 (C;C) = APOE3/APOE3 (Good), most common
If the allele of this SNP is "C" and the same chromosome also harbors the rs429358 "C" allele, the combination is known as an APOE-ε4 allele. The APOE-ε4 allele has a strong influence on the risk of Alzheimer's disease.
Many studies have estimated the level of risk, and it varies depending on age, sex, ethnicity, and other factors. One meta-analysis estimated the odds ratios for rs429358 (C;C) and rs7412 (C;C) individuals, compared to the more common rs429358 (T;T) and rs7412 (C;C) (ApoE3/ApoE3) homozygotes, to be 12x for late-onset Alzheimer's and 61x for early-onset disease [R].
Meta-analyses have also supported the association between the APOE-ε4 allele and somewhat increased risk for heart disease, with an odds ratio of 1.42 (CI: 1.26 – 1.61) [R].

The Minor "T" allele is associated with:

Decreased Alzheimer's risk.

When rs7412 and rs429358 are both T (for the two SNPs located on the same chromosome) this is known as the APOE2 allele. APOE2 indicates a reduced risk of Alzheimer's disease.

Population Alleles Frequency

ethhicity	frequency
African/African-American	0.1061
Latino/Admixed American	0.0416
Ashkenazi Jewish	0.0563
East Asian	0.0816
European	0.0821
Other (population not assigned)	0.0731

Frequently Asked Questions

Why Are Alleles for This SNP Different Elsewhere? Major vs. Reference Allele Is My Variant Good or Bad? SNP vs. Mutation

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