DNA analysis of genes (Polygenic risk) shows increased risk of 9 health problems (all 9 fought by Vitamin D) – Feb 2024

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Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations

Nature Medicine volume 30, pages 480–487 (2024) https://doi.org/10.1038/s41591-024-02796-z
Niall J. Lennon, Leah C. Kottyan, Christopher Kachulis, Noura S. Abul-Husn, Josh Arias, Gillian Belbin, Jennifer E. Below, Sonja I. Berndt, Wendy K. Chung, James J. Cimino, Ellen Wright Clayton, John J. Connolly, David R. Crosslin, Ozan Dikilitas, Digna R. Velez Edwards, QiPing Feng, Marissa Fisher, Robert R. Freimuth, Tian Ge, The GIANT Consortium, The All of Us Research Program, Joseph T. Glessner, Adam S. Gordon, Candace Patterson, …Eimear E. Kenny (80 authors)

100 to 1,000,000 gene SNPs

Varies of lot with race

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.
 Download the PDF from VitaminDWiki
Clipped from PDF
Various forms of PRSs are available to consumers through commercial platforms such as 23andMe, Myriad Genetics (riskScore), Allelica, Ambry Genetics, and others, and several noncommercial studies have explored the clinical use of PRSs in direct-to-participant models

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Note: The word VITAMIN does not occur once in the study

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Polygenic Risk Scores: Ready for Prime Time? (yes) Eric Topol Feb 2024

Polygenic Risk Scores: at 23andMe as of late 2023
Anxiety, Asthma, Atrial Fibrillation, Attention Deficit Hyperactivity Disorder (ADHD), Basal and Squamous Cell Carcinoma, Cat Allergy, Coronary Artery Disease, Diverticulitis, Dog Allergy, Eczema (Atopic Dermatitis), Fibromyalgia, Gallstones, Gestational Diabetes, Glaucoma, Gout, Hashimoto’s Disease, HDL Cholesterol, High Blood Pressure, Insomnia, Irritable Bowel Syndrome, Kidney Stones, LDL Cholesterol, Lupus, Melanoma, Migraine, Nearsightedness, Nonalcoholic Fatty Liver Disease, Obstructive Sleep Apnea, Panic Attacks, Polycystic Ovary Syndrome, Preeclampsia, Psoriasis, Restless Legs Syndrome, Rosacea, Seasonal Allergies, Severe Acne, Triglycerides, Uterine Fibroids

• Note: A majority of these health problems are associated with low vitamin D

 Download the 23andMe PDF from VitaminDWiki

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Overview Asthma and Vitamin D contains

• VitaminDWiki pages containing ASTHMA in title (164 as of Nov 2024)
• Asthma attacks reduced in half if Vitamin D level higher than 42 nanograms – RCT May 2014
  • Started with 100,000 IU loading dose and has standard-of-care Asthma drug
• Asthma may be treated by Vitamin D if more than 40 ng for 12 months – Sept 2018
• Those with Asthma or COPD had half the response to Vitamin D – March 2020
  • Those with Asthma need larger doses to get the same response.
  • Probably need gut-friendly Vitamin D
• CDC funded study: 1.3 X Asthma risk if vaccination contained aluminum – Sept 2022
• Asthma occurrence rate reduced 3X by Vitamin D – 8 study meta-analysis - Aug 2021
• Asthma in child 2.3 X more likely if both parents asthmatic (unless add Vitamin D) – VDAART Nov 2018
• Adult-onset asthma 2X more likely if low vitamin D and not hyperallergenic – May 2018
• Children had poor lung function if mothers had low vitamin D while pregnant – Nov 2022
• 26 health factors increase the risk of COVID-19 – all are proxies for low vitamin D
  • CDC list of high-risk for COVID-19 includes Asthma
• Child Asthma increased 2.1 X by antibiotics, Child milk allergy increased 4.4 X by PPI – April 2018
• Asthmatic children taking Corticosteroids had 2X more vitamin D intake, but lower levels – July 2017
• Traffic pollution increases asthma unless supplement with Vitamin D (mice) June 2018
• Childhood asthma problems eliminated for months by 600,000 IU of Vitamin D injection – June 2017
• Proof that Vitamin D Works 92 health problems prevented/treated as of Nov 2020
  • Asthma has been proven to be treated by Vitamin D in at least 4 random controlled trials
• Childhood asthma still reduced 4 months after 800 IU of Vitamin D daily - RCT Feb 2016
• Respiratory Disease exacerbations (Asthma, CF, COPD) may be treated by Vitamin D – July 2019
• Women with asthma 35X more likely to be vitamin D deficient – Oct 2013
• If high vitamin D during pregnancy the child is 5X less likely to get asthma
• Asthma is treated by Vitamin D – now they are trying to understand why – Feb 2015
• Increase in vitamin D deficiency may partially explain increases in asthma and allergies – Jan 2015
• Why deficiencies in vitamin D and magnesium are linked to asthma Magnesium allows muscles to relax
• Babies 3.6X more likely to go to hospital for asthma if asthmatic mother had low vitamin D while pregnant – June 2019
• The worse the bronchial asthma, the lower the vitamin D – Jan 2017 has the following chart

click on the chart to see the study

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VitaminDWiki – Atrial Fibrillation decreased by Vitamin D or Magnesium - many studies

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VitaminDWiki – Overview Breast Cancer and Vitamin D contains:

• 25 Meta-analyses of Vitamin D and Breast Cancer
    example: 2X reduction of deaths from Breast Cancer if have enough Vitamin D.
• Appears that having lots of Vitamin D will reduce by 3 X the chance of Breast Cancer
     wonder just how much more proof is needed
• Breast Cancer 4X more likely if have poor genes
•     Cancer - Breast category listing has 259 items along with related searches
• Breast Cancer treatment – Vitamin D was the most-popular supplement – Jan 2023
• Breast Cancer again associated with low vitamin D – 15th meta-analysis Sept 2020
• Vitamin D reduced Breast Cancer mortality in 9 out of 9 studies, yet still no consensus – April 2019
• Vitamin D both prevents and treats Breast Cancer – 2019

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VitaminDWiki – Chronic Kidney contains

Chronic Kidney Disease decreases Vitamin D level in 4 ways
4X more Chronic Kidney disease patients are now using vitamin D – March 2014
Vitamin D testers have different test results if there is chronic kidney disease – Sept 2019
Kidney dialysis often filters out vitamin D
Low vitamin D causes many health problems, such as weak bones
Want to have good Vitamin D levels to prevent CKD from causing other health problems
Higher vitamin D levels can treat CKD 50 ng   80 ng
Monthly dosing appears better than daily for CKD and many other health problems
CKD also decreases Vitamin K2-7
Form of vitamin D to be used; normal, Calcitriol, or synthetic
Non-oral form is often better for CKD ( topical, emulsion swished in mouth, patch cream, etc)

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VitaminDWiki – Cardiovascular category:

529 items In Cardiovascular category

Cardiovascular category is associated with other categories: Diabetes 31, Omega-3 31 , Vitamin K 25 , Intervention 22 . Mortality 20 , Skin - Dark 18 , Magnesium 17 , Calcium 14 , Hypertension 14 , Trauma and surgery 13 , Stroke 13 , Kidney 12 , Metabolic Syndrome 11 , Seniors 10 , Pregnancy 8 as of Aug 2022

• Overview Cardiovascular and vitamin D
• Cardiovascular Disease is treated by Vitamin D - many studies 39+ meta-analyses
• Coronary Artery Disease and Vitamin D - many studies 18+
• Cardiovascular problems reduced by Omega-3 - many studies 34+
• Arteries and Atherosclerosis and Vitamin D - many studies 71+
• Atrial Fibrillation decreased by Vitamin D or Magnesium - many studies 26+
• Statins and Vitamin D - many studies 25+
• Arterial Stiffness and Vitamins – only Vitamin D was found to help – meta-analysis Feb 2022
• Those raising Vitamin D above 30 ng were 1.4 X less likely to die of Heart Attack (VA 19 years) – Oct 2021
• Giving free vitamin D to every Iranian would pay for itself by just reducing CVD – Oct 2021
• Sudden Cardiac Arrest – 2.8 X higher risk if low vitamin D – 2019
• Peripheral arterial disease risk is 1.5X higher if low vitamin D – meta-analysis March 2018
• Heart attack ICU costs cut in half by Vitamin D – Oct 2018
• Cardiovascular disease 2.3 X more-likely if poor Vitamin D Receptor – Aug 2022

Cholesterol, Statins

• Cholesterol is needed to produce both Vitamin D and Cortisol
• Overview Cholesterol and vitamin D
• Statins and Vitamin D - many studies statins often reduce levels of vitamin D
• Statin side-effects are reduced by Vitamin D – US patent Application – April 2019

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Hypercholesterolemia and Vitamin D - Perplexity AI July 2024

See also VitaminDWiki

• Increased Vitamin D associated with decreased Cholesterol – Nov 2021

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VitaminDWiki - Overview Prostate Cancer and Vitamin D contains:

All items in category Prostate Cancer and Vitamin D 103 items

Examples

• Overview Prostate Cancer and Vitamin D
• Prostate Cancer long term survival 1.7 X more likely if high level of vitamin D – Jan 2016
• High PSA readings with Prostate Cancer 4 times more likely if poor Vitamin D receptor – March 2016
• Aggressive Prostate Cancer in blacks with low vitamin D – 7X more likely if added Calcium – Jan 2017
  • Probably better than 40% reduction if 40 ng of Vitamin D and minimize Calcium
• Prostate cancer in black men is 1.6 times more likely if a poor Vitamin D Receptor – Feb 2017
  • Probably better than 40% reduction if 40 ng of Vitamin D and improve Receptor activation (8 ways)
• Low-Grade Prostate Cancer 70 percent less likely to progress if good level of Omega-3 – June 2018
  • Might prevent Prostate Cancer with Omega-3 and Vitamin D
• Prostate Cancer PSA reduced by 60 ng of Vitamin D, Vitamin B complex, Omega-3, Curcumin and diet – June 2021
• The use of Vitamin D to prevent prostate cancer doubled in a decade – May 2019
• Prostate cancer patients in Jamaica were 5X more likely to die of PC if low vitamin D - Sept 2022
• Can take 40,000 IU of vitamin D daily before prostate cancer surgery – RCT March 2013

The Meta-analysis of Prostate Cancer

Vitamin D prevents/treats Prostate Cancer much better when there is not excess Calcium
Prostate cancer risk increase with Vitamin D (other studies disagree) – meta-analysis Jan 2018 prevention
Prostate cancer reduced when 4000 IU vitamin D was added– Hollis RCT April 2015 treatment
7X increase in stage IV Prostate Cancer survival when vitamin D greater than 32 ng – May 2013
Never too late to have vitamin D - loading dose is great before Prostate Surgery

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VitaminDWiki - T1 Diabetes 50+ studies

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VitaminDWiki – Overview Diabetes and vitamin D contains 490 T2D studies

• Diabetes is 5X more frequent far from the equator
• Children getting 2,000 IU of vitamin D are 8X less likely to get Type 1 diabetes
• Obese people get less sun / Vitamin D - and also vitamin D gets lost in fat
• Sedentary people get less sun / Vitamin D
• Worldwide Diabetes increase has been concurrent with vitamin D decrease and air conditioning
• Elderly get 4X less vitamin D from the same amount of sun
      Elderly also spend less time outdoors and have more clothes on
• All items in category Diabetes and Vitamin D 551 items: both Type 1 and Type 2

Vitamin D appears to both prevent and treat diabetes

• Appears that >2,000 IU will Prevent
• Appears that >4,000 IU will Treat , but not cure
• 90% less T2 Diabetes in the group having lots of Vitamin D
• Appears that Magnesium helps both Prevention and Treatment
• Many diabetics would be better treated if Gut-Friendly Vitamin D were used

Number of articles in both categories of Diabetes and:

• Dark Skin 24;   Intervention 56;   Meta-analysis 40;   Obesity 36;  Pregnancy 44;   T1 (child) 39;  Omega-3 11;  Vitamin D Receptor 24;  Genetics 13;  Magnesium 29    Click here to see details

Some Diabetes studies

• Take Vitamin D to prevent prediabetes from progressing into diabetes – American Diabetic Association – 2024
• Diabetes and Vitamin D meta-analyses - many studies 39+ as of Nov 2024
• 99.7% of people who got Diabetes had been regularly consuming food emulsifiers - May 2024
• Type 2 Diabetes treated by Vitamin D (often 50,000 IU weekly) – meta-analysis July 2023
• Diabetic inflammation synergistically decreased by Vitamin D and exercise – RCT June 2022
• Incidence of Type-2 Diabetes increased 3X in 30 years (by the way, Vitamin D helps) – July 2022
• Vitamin d treats Type II Diabetes in many ways (14 article review) - Sept 2021
• T2 Diabetes 30 percent more likely if poor Vitamin D Receptor – meta-analysis of 47 studies – July 2021

50 ng of Vitamin D fights Diabetes

• Saudi study defines normal Vitamin D level to be 50 to 70 ng (diabetes, etc.) - June 2020
• Diabetes 5X less likely if more than 50 ng of Vitamin D – April 2018

T1 Diabetes

• T1 Diabetes 3X lower risk if high vitamin D (over 40 ng) – Meta-analysis Nov 2020
• Type 1 Diabetes is prevented and treated by Vitamin D – review of 16 studies – Sept 2019
• Type 1 Diabetes prevention with Vitamin D and Omega-3 – Symposium April 2019

Pre-Diabetes

• 4X reduction in prediabetes progressing to T2D if more than 50 ng of vitamin D – RCT March 2023
• Prediabetes reduced by weekly 60,000 IU of Vitamin D – RCT Jan 2021
• Prediabetes 1.5 X more likely to go away if take Vitamin D – meta-analysis July 2020

Diabetes, Metabolic Syndrome and Magnesium - many studies
Diabetic Epidemic

• Step back to 1994. Suppose an epidemic struck the United States, causing blindness, kidney failure, and leg amputations in steadily increasing numbers.
  Suppose that in less than a decade's time, the epidemic had victimized one out of every eight people
  That epidemic is real, and its name is diabetes, now the nation's sixth leading cause of death.
  Chart from the web (2018?)