Rooted In Research

The gene variants we test and the nutrients we provide are rooted in the latest research and scientific findings. We only include variants with at least three studies showing gene-nutrient interaction in humans and have 400+ supporting independent studies. All vitamins and minerals are EFSA-described, one of the strictest governing bodies for nutrient claims.

Here are a few studies showing how our genetics and nutrients impact major health systems...

Heart Health

Baudhuin LM. Genetics of coronary artery disease: focus on genome-wide association studies. Am J Transl Res. 2009;1(3):221‐234. Published 2009 Mar 5.

Bilguvar K, Yasuno K, Niemelä M, et al. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40(12):1472‐1477. doi:10.1038/ng.240

Helgadottir A, Thorleifsson G, Magnusson KP, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40(2):217‐224. doi:10.1038/ng.72

Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491‐1493. doi:10.1126/science.1142842

Karvanen J, Silander K, Kee F, et al. The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. Genet Epidemiol. 2009;33(3):237‐246. doi:10.1002/gepi.20374

Aberle J, Evans D, Beil FU, Seedorf U. A polymorphism in the apolipoprotein A5 gene is associated with weight loss after short-term diet. Clin Genet. 2005;68(2):152‐154. doi:10.1111/j.1399-0004.2005.00463.x

Aouizerat BE, Kulkarni M, Heilbron D, et al. Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids. J Lipid Res. 2003;44(6):1167‐1173. doi:10.1194/jlr.M200480-JLR200

Dorfmeister B, Cooper JA, Stephens JW, et al. The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochim Biophys Acta. 2007;1772(3):355‐363. doi:10.1016/j.bbadis.2006.11.008

Regieli JJ, Jukema JW, Doevendans PA, et al. Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol. 2009;54(14):1238‐1245. doi:10.1016/j.jacc.2009.05.061

Hassan MA, Al-Attas OS, Hussain T, et al. The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects. Mol Cell Biochem. 2013;380(1-2):121‐128. doi:10.1007/s11010-013-1665-z

Real JT, Chaves FJ, Ejarque I, et al. Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population. Eur J Hum Genet. 2003;11(12):959‐965. doi:10.1038/sj.ejhg.5201079

Meriño-Ibarra E, Castillo S, Mozas P, et al. Screening of APOB gene mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Biol. 2005;77(5):663‐673.

Shen H, Damcott CM, Rampersaud E, et al. Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the old order amish. Arch Intern Med. 2010;170(20):1850‐1855. doi:10.1001/archinternmed.2010.384

Castillo S, Tejedor D, Mozas P, et al. The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia. Atherosclerosis. 2002;165(1):127‐135. doi:10.1016/s0021-9150(02)00190-9

Fan YM, Karhunen PJ, Levula M, et al. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death. Thromb J. 2008;6:17. Published 2008 Dec 30. doi:10.1186/1477-9560-6-17

Durst R, Jansen A, Erez G, et al. The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Atherosclerosis. 2006;189(2):443‐450. doi:10.1016/j.atherosclerosis.2006.01.001

Casas JP, Bautista LE, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects. Circulation. 2004;109(11):1359‐1365. doi:10.1161/01.CIR.0000121357.76910.A3

Rossi GP, Maiolino G, Zanchetta M, et al. The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients. J Am Coll Cardiol. 2006;48(6):1166‐1174. doi:10.1016/j.jacc.2006.05.046

Zhang K, Bai P, Shi S, et al. The G894T polymorphism on endothelial nitric oxide synthase gene is associated with increased coronary heart disease among Asia population: evidence from a Meta analysis. Thromb Res. 2012;130(2):192‐197. doi:10.1016/j.thromres.2012.02.015

Abdel-Aziz TA, Mohamed RH. Association of endothelial nitric oxide synthase gene polymorphisms with classical risk factors in development of premature coronary artery disease. Mol Biol Rep. 2013;40(4):3065‐3071. doi:10.1007/s11033-012-2380-7

Angotti E, Mele E, Costanzo F, Avvedimento EV. A polymorphism (G-->A transition) in the -78 position of the apolipoprotein A-I promoter increases transcription efficiency. J Biol Chem. 1994;269(26):17371‐17374.

Juo SH, Wyszynski DF, Beaty TH, Huang HY, Bailey-Wilson JE. Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am J Med Genet. 1999;82(3):235‐241.

Ordovas JM, Corella D, Cupples LA, et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr. 2002;75(1):38‐46. doi:10.1093/ajcn/75.1.38

Cai B, Zhang T, Zhong R, et al. Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. PLoS One. 2014;9(3):e89609. Published 2014 Mar 4. doi:10.1371/journal.pone.0089609

Olteanu H, Munson T, Banerjee R. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002;41(45):13378‐13385. doi:10.1021/bi020536s

Abilleira S, Bevan S, Markus HS. The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis. J Med Genet. 2006;43(12):897‐901. doi:10.1136/jmg.2006.040808

Zee RY, Bubes V, Shrivastava S, Ridker PM, Glynn RJ. Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach. Clin Chim Acta. 2009;402(1-2):189‐192. doi:10.1016/j.cca.2009.01.011

Zhao L, Li Y, Wu D, Ma T, Xia SY, Liu Z. Cx37 C1019T polymorphism may contribute to the pathogenesis of coronary heart disease. Genet Test Mol Biomarkers. 2014;18(7):497‐504. doi:10.1089/gtmb.2014.0034

Undas A, Brummel K, Musial J, Mann KG, Szczeklik A. Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation. 2001;104(22):2666‐2672. doi:10.1161/hc4701.099787

Weiss EJ, Bray PF, Tayback M, et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996;334(17):1090‐1094. doi:10.1056/NEJM199604253341703

Radovica I, Fridmanis D, Vaivade I, Nikitina-Zake L, Klovins J. The association of common SNPs and haplotypes in CETP gene with HDL cholesterol levels in Latvian population. PLoS One. 2013;8(5):e64191. Published 2013 May 13. doi:10.1371/journal.pone.0064191

Agirbasli M, Eren F, Agirbasli D, White MJ, Williams SM. Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort: lessons learned on LPL, CETP, LIPC, ABCA1, and SHBG. OMICS. 2013;17(12):636‐645. doi:10.1089/omi.2013.0066

Wang J, Wang LJ, Zhong Y, et al. CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population. Lipids Health Dis. 2013;12:176. Published 2013 Nov 27. doi:10.1186/1476-511X-12-176

Ashfield-Watt PA, Pullin CH, Whiting JM, et al. Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr. 2002;76(1):180‐186. doi:10.1093/ajcn/76.1.180

Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354(15):1578‐1588. doi:10.1056/NEJMoa055227

Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. BMJ. 2005;331(7524):1053. doi:10.1136/bmj.38611.658947.55

Jacques PF, Kalmbach R, Bagley PJ, et al. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr. 2002;132(2):283‐288. doi:10.1093/jn/132.2.283

Arking DE, Khera A, Xing C, et al. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. PLoS One. 2009;4(1):e4333. doi:10.1371/journal.pone.0004333

Crotti L, Monti MC, Insolia R, et al. NOS1AP is a genetic modifier of the long-QT syndrome. Circulation. 2009;120(17):1657‐1663. doi:10.1161/CIRCULATIONAHA.109.879643

Kao WH, Arking DE, Post W, et al. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation. 2009;119(7):940‐951. doi:10.1161/CIRCULATIONAHA.108.791723

Liu X, Pei J, Hou C, et al. A common NOS1AP genetic polymorphism, rs12567209 G>A, is associated with sudden cardiac death in patients with chronic heart failure in the Chinese Han population. J Card Fail. 2014;20(4):244‐251. doi:10.1016/j.cardfail.2014.01.006

Eijgelsheim M, Newton-Cheh C, Aarnoudse AL, et al. Genetic variation in NOS1AP is associated with sudden cardiac death: evidence from the Rotterdam Study. Hum Mol Genet. 2009;18(21):4213‐4218. doi:10.1093/hmg/ddp356

Aarnoudse AJ, Newton-Cheh C, de Bakker PI, et al. Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam Study. Circulation. 2007;116(1):10‐16. doi:10.1161/CIRCULATIONAHA.106.676783

Arking DE, Pfeufer A, Post W, et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet. 2006;38(6):644‐651. doi:10.1038/ng1790

Marjamaa A, Newton-Cheh C, Porthan K, et al. Common candidate gene variants are associated with QT interval duration in the general population. J Intern Med. 2009;265(4):448‐458. doi:10.1111/j.1365-2796.2008.02026.x

Nakajima T, Jorde LB, Ishigami T, et al. Nucleotide diversity and haplotype structure of the human angiotensinogen gene in two populations. Am J Hum Genet. 2002;70(1):108‐123. doi:10.1086/338454

Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992;71(1):169‐180. doi:10.1016/0092-8674(92)90275-h

Corvol P, Jeunemaitre X. Molecular genetics of human hypertension: role of angiotensinogen. Endocr Rev. 1997;18(5):662‐677. doi:10.1210/edrv.18.5.0312

Johnson AD, Newton-Cheh C, Chasman DI, et al. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension. 2011;57(5):903‐910. doi:10.1161/HYPERTENSIONAHA.110.158667

Siffert W. G-protein beta3 subunit 825T allele and hypertension. Curr Hypertens Rep. 2003;5(1):47‐53. doi:10.1007/s11906-003-0010-4

Selenium

Bastaki M, Huen K, Manzanillo P, et al. Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Pharmacogenet Genomics. 2006;16(4):279‐286. doi:10.1097/01.fpc.0000199498.08725.9c

Tang TS, Prior SL, Li KW, et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012;22(5):417‐425. doi:10.1016/j.numecd.2010.08.001

Bhatti P, Stewart PA, Hutchinson A, et al. Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1841‐1848. doi:10.1158/1055-9965.EPI-09-0197

Xiong YM, Mo XY, Zou XZ, et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010;18(6):817‐824. doi:10.1016/j.joca.2010.02.004

Soerensen M, Christensen K, Stevnsner T, Christiansen L. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev. 2009;130(5):308‐314. doi:10.1016/j.mad.2009.01.005

Steinbrecher A, Méplan C, Hesketh J, et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010;19(11):2958‐2968. doi:10.1158/1055-9965.EPI-10-0364

Chen J, Cao Q, Qin C, et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011;137(10):1553‐1561. doi:10.1007/s00432-011-1033-x

Karunasinghe N, Han DY, Zhu S, et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012;7(2):179‐190. doi:10.1007/s12263-011-0259-1

Hong Z, Tian C, Zhang X. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013;40(2):1801‐1812. doi:10.1007/s11033-012-2234-3

Jablonska E, Gromadzinska J, Reszka E, et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009;48(6):383‐386. doi:10.1007/s00394-009-0023-0

Bone Health

Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone. 2003;32(6):711‐717. doi:10.1016/s8756-3282(03)00087-5

Jin H, Evangelou E, Ioannidis JP, Ralston SH. Polymorphisms in the 5' flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteoporos Int. 2011;22(3):911‐921. doi:10.1007/s00198-010-1364-5

Qureshi AM, Herd RJ, Blake GM, Fogelman I, Ralston SH. COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy. Calcif Tissue Int. 2002;70(3):158‐163. doi:10.1007/s00223-001-1035-9

Palomba S, Orio F Jr, Russo T, et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporos Int. 2005;16(8):943‐952. doi:10.1007/s00198-004-1800-5

Jia F, Sun RF, Li QH, et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers. 2013;17(1):30‐34. doi:10.1089/gtmb.2012.0267

Palomba S, Numis FG, Mossetti G, et al. Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes. Hum Reprod. 2003;18(1):192‐198. doi:10.1093/humrep/deg031

Creatsa M, Pliatsika P, Kaparos G, et al. The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: a pilot study. J Obstet Gynaecol Res. 2011;37(10):1415‐1422. doi:10.1111/j.1447-0756.2011.01557.x

Mossetti G, Gennari L, Rendina D, et al. Vitamin D receptor gene polymorphisms predict acquired resistance to clodronate treatment in patients with Paget's disease of bone. Calcif Tissue Int. 2008;83(6):414‐424. doi:10.1007/s00223-008-9193-7

Gennari L, Merlotti D, De Paola V, et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol. 2005;161(4):307‐320. doi:10.1093/aje/kwi055

van Meurs JB, Schuit SC, Weel AE, et al. Association of 5' estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet. 2003;12(14):1745‐1754. doi:10.1093/hmg/ddg176

Herrington DM, Howard TD, Hawkins GA, et al. Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. N Engl J Med. 2002;346(13):967‐974. doi:10.1056/NEJMoa012952

Herrington DM, Howard TD, Brosnihan KB, et al. Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein [published correction appears in Circulation. 2003 Jul 29;108(4):5001]. Circulation. 2002;105(16):1879‐1882. doi:10.1161/01.cir.0000016173.98826.88

Koek WN, van Meurs JB, van der Eerden BC, et al. The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake. J Bone Miner Res. 2010;25(9):1980‐1987. doi:10.1002/jbmr.83

Matlik L, Savaiano D, McCabe G, VanLoan M, Blue CL, Boushey CJ. Perceived milk intolerance is related to bone mineral content in 10- to 13-year-old female adolescents. Pediatrics. 2007;120(3):e669‐e677. doi:10.1542/peds.2006-1240

Metabolism Health

Lyssenko V, Lupi R, Marchetti P, et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155‐2163. doi:10.1172/JCI30706

Cauchi S, Froguel P. TCF7L2 genetic defect and type 2 diabetes. Curr Diab Rep. 2008;8(2):149‐155. doi:10.1007/s11892-008-0026-x

Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism. 2007;56(9):1174‐1178. doi:10.1016/j.metabol.2007.04.012

Saber-Ayad M, Manzoor S, El Serafi A, et al. The FTO rs9939609 "A" allele is associated with impaired fasting glucose and insulin resistance in Emirati population. Gene. 2019;681:93‐98. doi:10.1016/j.gene.2018.09.053

van Vliet-Ostaptchouk JV, Onland-Moret NC, van Haeften TW, et al. HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008;16(5):652‐656. doi:10.1038/sj.ejhg.5202008

Omori S, Tanaka Y, Takahashi A, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008;57(3):791‐795. doi:10.2337/db07-0979

Furukawa Y, Shimada T, Furuta H, et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008;93(1):310‐314. doi:10.1210/jc.2007-1029

Huth C, Heid IM, Vollmert C, et al. IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes. 2006;55(10):2915‐2921. doi:10.2337/db06-0600

Illig T, Bongardt F, Schöpfer A, et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes [published correction appears in J Clin Endocrinol Metab. 2005 Dec;90(12):6385]. J Clin Endocrinol Metab. 2004;89(10):5053‐5058. doi:10.1210/jc.2004-0355

Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369‐1376. doi:10.1172/JCI2629

Bai H, Jing D, Guo A, Yin S. Association between interleukin 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population [published correction appears in J Int Med Res. 2014 Oct;42(5):1189]. J Int Med Res. 2014;42(3):702‐710. doi:10.1177/0300060513505813

Scarpelli D, Cardellini M, Andreozzi F, et al. Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in caucasian italian subjects. Diabetes. 2006;55(5):1529‐1533. doi:10.2337/db06-0047

Gouda HN, Sagoo GS, Harding AH, Yates J, Sandhu MS, Higgins JP. The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am J Epidemiol. 2010;171(6):645‐655. doi:10.1093/aje/kwp450

Altshuler D, Hirschhorn JN, Klannemark M, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26(1):76‐80. doi:10.1038/79216

Deeb SS, Fajas L, Nemoto M, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998;20(3):284‐287. doi:10.1038/3099

Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889‐894. doi:10.1126/science.1141634

Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661‐678. doi:10.1038/nature05911

Hertel JK, Johansson S, Raeder H, et al. Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia. 2008;51(6):971‐977. doi:10.1007/s00125-008-0982-3

Florez JC, Jablonski KA, Kahn SE, et al. Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes. 2007;56(2):531‐536. doi:10.2337/db06-0966

Zhou D, Zhang D, Liu Y, et al. The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population. J Hum Genet. 2009;54(7):433‐435. doi:10.1038/jhg.2009.54

Omori S, Tanaka Y, Takahashi A, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008;57(3):791‐795. doi:10.2337/db07-0979

Florez JC, Burtt N, de Bakker PI, et al. Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 2004;53(5):1360‐1368. doi:10.2337/diabetes.53.5.1360

Detoxification Ability

McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner WD. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 1995;4(6):589‐594.

Sreeja L, Syamala V, Hariharan S, et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008;7(1):73‐85.

Funke S, Risch A, Nieters A, et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009;2009:302047. doi:10.1155/2009/302047

Miller DP, Asomaning K, Liu G, et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006;107(7):1570‐1577. doi:10.1002/cncr.22124

Sutton A, Imbert A, Igoudjil A, et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics. 2005;15(5):311‐319. doi:10.1097/01213011-200505000-00006

Stücker I, Hirvonen A, de Waziers I, et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002;23(9):1475‐1481. doi:10.1093/carcin/23.9.1475

Free Radical Protection

McWilliams JE, Sanderson BJ, Harris EL, Richert-Boe KE, Henner WD. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 1995;4(6):589‐594.

Sreeja L, Syamala V, Hariharan S, et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008;7(1):73‐85.

Funke S, Risch A, Nieters A, et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009;2009:302047. doi:10.1155/2009/302047

Miller DP, Asomaning K, Liu G, et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006;107(7):1570‐1577. doi:10.1002/cncr.22124

Sutton A, Imbert A, Igoudjil A, et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics. 2005;15(5):311‐319. doi:10.1097/01213011-200505000-00006

Stücker I, Hirvonen A, de Waziers I, et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002;23(9):1475‐1481. doi:10.1093/carcin/23.9.1475

Tang TS, Prior SL, Li KW, et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012;22(5):417‐425. doi:10.1016/j.numecd.2010.08.001

Bhatti P, Stewart PA, Hutchinson A, et al. Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1841‐1848. doi:10.1158/1055-9965.EPI-09-0197

Brain Health

Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278(16):1349‐1356.

Tang MX, Stern Y, Marder K, et al. The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998;279(10):751‐755. doi:10.1001/jama.279.10.751

Noguchi-Shinohara M, Abe C, Yuki-Nozaki S, et al. Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study. J Alzheimers Dis. 2018;63(4):1289‐1297. doi:10.3233/JAD-170971

Majewicz J, Rimbach G, Proteggente AR, Lodge JK, Kraemer K, Minihane AM. Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers. Biochem Biophys Res Commun. 2005;338(2):951‐955. doi:10.1016/j.bbrc.2005.10.029

Huebbe P, Lodge JK, Rimbach G. Implications of apolipoprotein E genotype on inflammation and vitamin E status. Mol Nutr Food Res. 2010;54(5):623‐630. doi:10.1002/mnfr.200900398

Mas E, Dupuy AM, Artero S, et al. Functional Vitamin E deficiency in ApoE4 patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2006;21(3):198‐204. doi:10.1159/000090868

D'Cunha NM, Georgousopoulou EN, Boyd L, et al. Relationship Between B-Vitamin Biomarkers and Dietary Intake with Apolipoprotein E є4 in Alzheimer's Disease. J Nutr Gerontol Geriatr. 2019;38(2):173‐195. doi:10.1080/21551197.2019.1590287

Köbe T, Witte AV, Schnelle A, et al. Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment. Am J Clin Nutr. 2016;103(4):1045‐1054. doi:10.3945/ajcn.115.116970

R Cardoso B, Hare DJ, Lind M, et al. The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease. ACS Chem Neurosci. 2017;8(7):1459‐1464. doi:10.1021/acschemneuro.7b00014

Gao S, Jin Y, Hall KS, et al. Selenium level is associated with apoE epsilon4 in rural elderly Chinese. Public Health Nutr. 2009;12(12):2371‐2376. doi:10.1017/S1368980009005102

Homocysteine

Ashfield-Watt PA, Pullin CH, Whiting JM, et al. Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr. 2002;76(1):180‐186. doi:10.1093/ajcn/76.1.180

Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354(15):1578‐1588. doi:10.1056/NEJMoa055227

Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. BMJ. 2005;331(7524):1053. doi:10.1136/bmj.38611.658947.55

Jacques PF, Kalmbach R, Bagley PJ, et al. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr. 2002;132(2):283‐288. doi:10.1093/jn/132.2.283

Andreassi MG, Botto N, Maffei S. Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening. Clin Chem Lab Med. 2006;44(5):514‐521. doi:10.1515/CCLM.2006.103

Fermo I, Vigano' D'Angelo S, Paroni R, Mazzola G, Calori G, D'Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease. Ann Intern Med. 1995;123(10):747‐753. doi:10.7326/0003-4819-123-10-199511150-00002

U.S. Food and Drug Administration. Food Standards: Amendment of Standards of Identity for Enriched Grain Products to Require Addition of Folic Acid: Final Rule. 21 CFR Parts 136, 137, and 139. Federal Register 1996;61(44):8781-97.

Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014;44(5):480‐488. doi:10.3109/00498254.2013.845705

van der Put NM, Gabreëls F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am J Hum Genet. 1998;62(5):1044‐1051. doi:10.1086/301825

Stead LM, Au KP, Jacobs RL, Brosnan ME, Brosnan JT. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am J Physiol Endocrinol Metab. 2001;281(5):E1095‐E1100. doi:10.1152/ajpendo.2001.281.5.E1095

Walker JB. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol. 1979;50:177‐242. doi:10.1002/9780470122952.ch4

Zeisel S. Choline, Other Methyl-Donors and Epigenetics. Nutrients. 2017;9(5):445. Published 2017 Apr 29. doi:10.3390/nu9050445

Chango A, Boisson F, Barbé F, et al. The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br J Nutr. 2000;83(6):593‐596. doi:10.1017/s0007114500000751

Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998;64(3):169‐172. doi:10.1006/mgme.1998.2714

Lievers KJ, Boers GH, Verhoef P, et al. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). 2001;79(9):522‐528. doi:10.1007/s001090100253

Prasad K. Homocysteine, a Risk Factor for Cardiovascular Disease. Int J Angiol. 1999;8(1):76‐86. doi:10.1007/BF01616850

Eye Health

Yang Z, Camp NJ, Sun H, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314(5801):992‐993. doi:10.1126/science.1133811

Chen W, Xu W, Tao Q, et al. Meta-analysis of the association of the HTRA1 polymorphisms with the risk of age-related macular degeneration. Exp Eye Res. 2009;89(3):292‐300. doi:10.1016/j.exer.2008.10.017

Dewan A, Liu M, Hartman S, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006;314(5801):989‐992. doi:10.1126/science.1133807

Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385‐389. doi:10.1126/science.1109557

Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005;308(5720):419‐421. doi:10.1126/science.1110359

Fritsche LG, Loenhardt T, Janssen A, et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet. 2008;40(7):892‐896. doi:10.1038/ng.170

Rivera A, Fisher SA, Fritsche LG, et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet. 2005;14(21):3227‐3236. doi:10.1093/hmg/ddi353

Ross RJ, Bojanowski CM, Wang JJ, et al. The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci. 2007;48(3):1128‐1132. doi:10.1167/iovs.06-0999

Omega-3 Processing

Angotti E, Mele E, Costanzo F, Avvedimento EV. A polymorphism (G-->A transition) in the -78 position of the apolipoprotein A-I promoter increases transcription efficiency. J Biol Chem. 1994;269(26):17371‐17374.

Juo SH, Wyszynski DF, Beaty TH, Huang HY, Bailey-Wilson JE. Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am J Med Genet. 1999;82(3):235‐241.

Ordovas JM, Corella D, Cupples LA, et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr. 2002;75(1):38‐46. doi:10.1093/ajcn/75.1.38

CoQ10 Processing

Fischer A, Schmelzer C, Rimbach G, Niklowitz P, Menke T, Döring F. Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans. BMC Res Notes. 2011;4:245. Published 2011 Jul 21. doi:10.1186/1756-0500-4-245

Freriksen JJ, Salomon J, Roelofs HM, et al. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer. J Hum Genet. 2014;59(7):381‐386. doi:10.1038/jhg.2014.38

Yu H, Liu H, Wang LE, Wei Q. A functional NQO1 609C>T polymorphism and risk of gastrointestinal cancers: a meta-analysis. PLoS One. 2012;7(1):e30566. doi:10.1371/journal.pone.0030566

Yadav U, Kumar P, Rai V. "NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis.". Nutr Cancer. 2018;70(4):557‐568. doi:10.1080/01635581.2018.1460674

Ding R, Lin S, Chen D. Association of NQO1 rs1800566 polymorphism and the risk of colorectal cancer: a meta-analysis. Int J Colorectal Dis. 2012;27(7):885‐892. doi:10.1007/s00384-011-1396-0

Iron Needs

Vujić M. Molecular basis of HFE-hemochromatosis. Front Pharmacol. 2014;5:42. Published 2014 Mar 11. doi:10.3389/fphar.2014.00042

Carella M, D'Ambrosio L, Totaro A, et al. Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Am J Hum Genet. 1997;60(4):828‐832.

Mura C, Raguenes O, Férec C. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood. 1999;93(8):2502‐2505.

Aranda N, Viteri FE, Montserrat C, Arija V. Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain. Ann Hematol. 2010;89(8):767‐773. doi:10.1007/s00277-010-0901-9

Joint Health

Dayer JM. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology (Oxford). 2003;42 Suppl 2:ii3‐ii10. doi:10.1093/rheumatology/keg326

Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology (Oxford). 2003;42 Suppl 2:ii11‐ii16. doi:10.1093/rheumatology/keg327

Oregón-Romero E, Vázquez-Del Mercado M, Ruiz-Quezada SL, et al. Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNF-alpha. J Investig Med. 2008;56(7):937‐943. doi:10.2310/JIM.0b013e318189152b

Virtanen IM, Karppinen J, Taimela S, et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine (Phila Pa 1976). 2007;32(10):1129‐1134. doi:10.1097/01.brs.0000261473.03274.5c

Calcium Needs

Koek WN, van Meurs JB, van der Eerden BC, et al. The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake. J Bone Miner Res. 2010;25(9):1980‐1987. doi:10.1002/jbmr.83

Obermayer-Pietsch BM, Bonelli CM, Walter DE, et al. Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J Bone Miner Res. 2004;19(1):42‐47. doi:10.1359/JBMR.0301207

Travis RC, Appleby PN, Siddiq A, et al. Genetic variation in the lactase gene, dairy product intake and risk for prostate cancer in the European prospective investigation into cancer and nutrition. Int J Cancer. 2013;132(8):1901‐1910. doi:10.1002/ijc.27836

Enattah N, Pekkarinen T, Välimäki MJ, Löyttyniemi E, Järvelä I. Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women. Eur J Clin Nutr. 2005;59(10):1105‐1111. doi:10.1038/sj.ejcn.1602219