GWAS NCBI db Ga P http www ncbi
GWAS • 対象疾患 – NCBI db. Ga. P 登録疾患リスト • • http: //www. ncbi. nlm. nih. gov/entrez/query/Gap/gap_tmpl/about. html Disease Studies Variables Documents Participants Type of Study Aging Alzheimer Disease Cardiovascular Disease Death Dementia Hypertension Obesity 12 -------- Aging Alzheimer Disease Dementia 2 ----- Amyotrophic Lateral Sclerosis 2 ------- Amyotrophic Lateral Sclerosis Bulbar Palsy, Progressive Motor Neuron Disease Muscular Atrophy, Spinal 1 ---- Angina Pectoris Congestive Heart Failure Coronary Disease Intermittent Claudication Ischemic Attack, Transient Myocardial Infarction Stroke 1 ---- Angina Pectoris Death Heart Failure, Congestive Intermittent Claudication Ischemic Attack, Transient Myocardial Infarction Stroke 1 ---- Asthma 1 ------- Atherosclerosis Cardiomyopathies Heart Failure Hypertrophy, Left Ventricular 1 ---- Atherosclerosis Stroke 2 ----- Atrial Fibrillation Atrial Flutter 1 ---Attention Deficit Disorder with Hyperactivity 1 ---- Bipolar Disorder 1 ---- Bone Density Bones of Lower Extremity Metacarpal Bones Muscles, Skeletal Osteoporosis 1 ---- Brain Infarction Cerebrovascular Accident Cerebrovascular Disease Intracranial Aneurysm Intracranial Arteriovenous Malformations Ischemic Attack, Transient 1 ---- Brain Ischemia Cerebrovascular Accident Cerebrovascular Disorders 1 --- Cardiovascular Disease 1 ---- Cardiovascular Disease Muscular Disease Rhabdomyolysis 1 ----Cardiovascular System Cerebrovascular Accident Cholesterol Dementia Diabetes Mellitus Heart Diseases Heart Failure, Congestive Hypertension Intermittent Claudication Myocardial Infarction Obesity Osteoporosis Risk Factors Smoking 1 ---- Cataract Glaucoma Macular Degeneration Retinopathy 1 ---- Cataract Macular Degeneration 1 ---- Coronary Artery Bypass Heart Valve Prosthesis Implantation 1 ---- Coronary Disease 1 ---- Dementia 2 ----- Diabetes Mellitus, Type 21 ----- Diabetic Nephropathy 1 ---- Fatty Liver 1 ---- Heart Failure Stroke 1 ---- Hormone Replacement Therapies Hysterectomy Menopause 1 ---- Ischemic Attack, Transient Stroke 1 ---- Lupus Erythematosus, Systemic 1 ------- Major Depressive Disorder 1 ---- Neuroblastoma 1 ----- Osteoarthritis 1 --- Parkinson Disease 4 ------- Psoriasis Psoriatic Arthritis 1 ---- Pulmonary Disease 1 ---- Schizophrenia 1 ---Sleep Apnea Syndromes Sleep Apnea, Obstructive 1 ---- Stroke 1 ---
スタディの結果 「関連遺伝子」の強さ • p値 • オッズ比・相対危険度 • Genotypic attributable risk • Genotype-Specific Recurrence Risks – Genotype-Specific Recurrence Risks as Indicators of the Genetic Architecture of Complex Diseases. by Slatkin. Am J Hum Genet 83, 120 -126, 2008
Korean 民族差
Central Dogma & DNA Variations DNA Variations Transcription initiation point Transcription termination point Variations Splicing and m. RNA maturation Variations m. RNA Translation initiation point Translation Codon triplets Variations Translation termination point Peptide Post-translational peptide modifications Molecules
Not one way, but Multiple Bifurcations Sequence (qualitative) variations, quantitative variations, Chrono-spatial variations DNA mRNA2 Transcript variations mRNA1 Peptide variations Molecular variations Peptide3 Peptide1 Peptide2 Molecule3 Molecule1 Molecule2 Molecule4
Association study with DNA-markers Susceptible DNA-m. RNA-Protein relation is not straight, but comparison between DNA variations and phenotype variations bypassing m. RNA/proteins simplifies the analysis structure. Non-susceptible
Non-coding-gene World and Variations DNA Effects on transcription Coding DNA Functional RNA Coding m. RNA Effects on translation ? ? Effects on phenotypes? ? Coding-gene World and Variations
ヒトゲノムサイズ 1 10 102 103 104 105 106 107 108 109 Sub-microscopic variants Microscopic variants Structural variants SNP ♂♀ 置換型多型 挿入欠失型 CNV リピート型 向きの多型(逆位) 位置の多型(転座) 1010
Genotyping technologies and further developments • • 100, 000 marker-panel 250, 000 marker-panel 500, 000 marker-panel … 1, 000 marker-panel … … Whole genome typing of all samples Typing
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