AskSia - POPH90111

2）你“必须背熟”的核心术语/定义清单（按模块流水线）

UNDERSTAND（M1–M2）

Familial aggregation（家族聚集性）：家族内疾病聚集超过偶然；证据但非证明，共享环境是竞争解释。[7]Source: asksia-bible-poph90111-bilingual.pdfEN + 中文 Bilingual glossary - every examinable term 双语术语表:每个可考术语 English term . X . one-line meaning - grouped along the UNDERSTAND -> DISCOVER- CHARACTERISEUSE pipeline 英文术语 · 中文 · 一句话释义 -- 沿理解→ 发现→刻画→ 应用的流程分组 A fast reference for the vocabulary POPH90111 actually examines 〔本课程实际考查的术语速查〕. About 50 terms across the eight-module spine, each with a one-line English meaning; the middle column is reserved for the standard Chinese translation added in the bilingual pass. Cover the right column and recite the meaning from the term - then flip and recall the term from the meaning. POPH90111 实际考查术语的速查表〔本课程实际考查的术语速查〕。横跨八个模块主干约50个术语,每个配一行英文释义;中间一列留给双语版加入的标准中文译名。遮住右列,由术语复述释义 -- 再翻过来,由释义回忆术语。 Term (EN) 中文 One-line meaning Foundations - genetics vocabulary Locus / allele — A fixed position on a chromosome / the specific DNA base(s) present there; the minor allele is the rarer one. Genotype — The pair of alleles a person carries at a locus (TT, TC, CC); homozygous = identical, heterozygous = different. SNP — Single-nucleotide polymorphism - a common single-base variant (>1% frequency); the workhorse marker of GWAS. Polymorphism vs mutation — Polymorphism = common, little/no deleterious effect; (pathogenic) mutation = major deleterious effect - substantial risk. Germline vs somatic — Germline = inherited, in every cell - relevant to familial risk; somatic = acquired, in descendant cells only (e. g. a tumour clone). Allele frequency p — Proportion of all alleles at a locus that are the allele of interest: p = [2. n(AA)+n(Aa)]/(2N); per- chromosome (denominator 2N). Carrier frequency — Proportion of people carrying ≥1 risk allele = p2 + 2pq = 1 - q2; per-person (denominator N). Sets exposure prevalence & power. Hardy-Weinberg equilibrium — In a large randomly-mating population with no selection/migration/mutation: AA=p2, Aa=2pq, aa=q2 (p2+2pq+q2=1), constant across generations. HWE x2 test — Goodness-of-fit x2=(O-E)2/E over 3 genotypes, df=1; deviation in controls flags genotyping error / stratification. Module 1 - Familial aggregation (UNDERSTAND) Familial aggregation — Disease clusters in families more than chance; evidence for, not proof of, a genetic cause (shared environment is the rival).[1]Source: asksia-bible-poph90111-bilingual.pdfA 1 . LEARN 1· 学习 You haven't watched the module yet. Read a chapter top to bottom. Every concept is an AHA-unit: diagram - explainer + method-in-steps - analogy + trap. The figures are original schematics of the standard genetic-epi canon - learn the idea cold before the numbers. 你还没看过该模块。从头到尾读一章。每个概念都是一个 AHA 单元:图示→讲解→ 分步方法 →类比→陷阱。图均为标准遗传流行病学经典内容的原创示意图 -- 先把思路彻底吃透,再上数字。 B 2 . DRILL 2 · 演练 You've watched the module and done the Q&A. Cover the worked steps and re-derive each OR, RR, SMR, h2, penetrance and NNT by hand. Then say aloud the interpretation and the one bias that would change your conclusion. 你已看过该模块并做完 Q&A。遮住已演算的步骤,亲手重新推导每一个 OR、RR、SMR、h2、外显率和 NNT。然后大声说出解读,以及那一个会改变你结论的偏倚。 C 3 . ASSIGNMENT 3 · 作业 The assignment is open. Use the design-appraisal grids and worked-formula boxes as your lookup. Every question is calculate - interpret -+ appraise; the Stata . do file (A1 Q1) does the arithmetic, but the interpretation and appraisal marks are yours to write. 作业是开卷的。把设计评价表格和公式演算框当作你的查阅工具。每道题都是计算→解读→ 评价;Stata 的 . do 文件(A1 Q1)负责算术,但解读和评价的分数要你自己写出来。 POPH90111 . Genetic Epidemiology ! The single most important thing to understand about POPH90111 关于 POPH90111 最重要的一点认识 This subject is a logical pipeline, not a pile of topics: UNDERSTAND (is there a genetic role? - familial aggregation M1, heritability M2) - DISCOVER (which variants? - association/GWAS M3) - CHARACTERISE (how risky? - penetrance M5, modifiers M6, G×E M7) - USE IN PRACTICE (causal exposures via MR M4, screening M8). One mantra recurs at every stage: familial aggregation / high MZ-vs-DZ correlation is 'evidence for, but not proof of, an inherited genetic aetiology' - shared environment is always the rival explanation. Write that sentence whenever you interpret aggregation or heritability. 本科目是一条逻辑流水线,而非一堆零散主题:理解(是否存在遗传作用?→家族聚集性 M1、遗传力 M2)→发现 (哪些变异?→关联/GWAS M3)→刻画(风险有多大?→外显率M5、修饰因子 M6、GxE M7)→实践应用(经 MR 评估因果暴露 M4、筛查 M8)。一句口诀贯穿每一阶段:家族聚集性/高的 MZ-对-DZ 相关是“支持遗传性病因的证据,但非证明” -- 共享环境永远是竞争性解释。每当你解读聚集性或遗传力时都写下这句话。 i How this book was built - and the two-layer rule 本书如何编成 -- 以及两层规则 Standard genetic and statistical canon (Hardy-Weinberg, LD measures, Falconer's h2, the ACE model, Manhattan/QQ plots, MR's three IV assumptions, NNT/NNS) is stated plainly - it is universal, non-copyrightable science, and every diagram here is our own clean drawing. The course's specific framing and its lecturer's example numbers are paraphrased and re-checked, never copied from slides. The subject runs on A/Prof Aung Ko Win's modules with Prof Mark Jenkins' lectures; verify dates and weights against your own Canvas (the LMS), as cohort details can shift. 标准的遗传学与统计学经典(Hardy-Weinberg、LD 测度、Falconer h2、ACE 模型、曼哈顿图/QQ 图、MR 三个 IV 假设、NNT/NNS)均平实陈述 -- 它们是普适的、不受版权保护的科学,此处每张图都是我们自己干净的绘制。本课程特定的表述及其讲师的示例数字均为转述并重新核对,绝不照搬幻灯片。本科目以 A/Prof Aung Ko Win 的模块和 Prof Mark Jenkins 的讲课为基础;请对照你自己的 Canvas(即 LMS)核实日期与权重,因为各届的细节可能变动。 POPH90111 . Genetic Epidemiology THE BLUEPRINT - THE ASSESSMENT BLUEPRINT 90% IN TWO ASSIGNMENTS Three take-home pieces, no exam 三份带回家作业,无考试

Heritability（遗传率）：表型方差中归因于遗传方差的比例；人群+环境特异，非个体属性。[10]Source: asksia-bible-poph90111-bilingual.pdf★ What the assignment / exam asks here 此处作业/考试考什么 (1) Partition variance: given Va, Vd, Ve compute narrow-sense h2 = Va/Vp and broad-sense H2 = Vg/Vp. (2) From twin correlations apply Falconer: h2 = 2(rMZ - rDZ) and interpret. (3) Solve the ACE system for A, C, E from rMZ and rDZ. (4) Convert SD - variance (Vp = SD2) and explain estimating separately by sex and zygosity. (5) Explain the liability-threshold model for a binary trait. (6) The marks-rich part: critically appraise - equal-environments assumption, 'evidence for not proof of', missing heritability, what heritability does not mean. (1)分解方差:给定 Va、Vd、Ve,计算狭义 h2 = Va/Vp 和广义 H2 = Vg/Vp。(2)由双生子相关应用 Falconer: h2= 2(rMZ - rDZ) 并解读。(3)由 rMZ 和 rDZ 求解 ACE 方程组得 A、C、E。(4)把 SD→方差(Vp= SD2)并解释为何要按性别和合子性分别估计。(5)解释二分性状的易感性阈值模型。(6)富含分数的部分:严格评价一 -等环境假设、“是证据而非证明”、缺失遗传力,以及遗传力不意味着什么。 2. 1 Heritability is a proportion of variance 2. 1 遗传率是方差的一个比例 Start from the definition the course insists on. Heritability is the proportion of the phenotypic variance in a population that is attributable to genetic variance. The key word is variance - we are explaining differences between people, not the trait value of any one person. Variance is the spread, the squared standard deviation: V = SD2. 从课程坚持采用的定义出发。遗传率是一个人群中表型方差里可归因于遗传方差的比例。关键词是方差 -- 我们解释的是人与人之间的差异,而非任何一个人的性状取值。方差即离散度,是标准差的平方:V= SD2。 POPH90111 . Genetic Epidemiology VARIANCE PARTITION Top split: Vp = VG + VE Genetic split: VG = VA + Vp (+ VI) Broad-sense: H2 = VG / Vp Narrow-sense: h2 = VA / Vp (always h2 ≤ Hº) VA additive (allele effects sum - the part that passes parent-child); Vp dominance (interaction within a locus); VI epistasis (between loci); VE environment. VA 加性(等位基因效应相加 -- 可由亲代→子代传递的那部分);VD 显性(同一位点内部的交互);V1上位(位点之间);VE 环境。 D2 Fig 2. 1 - Family resemblance is fed by shared genes AND shared environment. Heritability is our attempt to read off the genetic slice of the variance - but the two sources are confounded, which is exactly why we need twins. Shared GENES(degree of relatedness)closer kin share more DNAShared ENVIRONMENTdiet, lifestyle, exposuresfamilies live alikeFamily resemblance(observed familial aggregation)aggregation = genes + shared env + chanceDegrees of relatedness1st parent/sib/childshare 1/22nd grandparent/uncleshare 1/43rd first cousinshare 1/8Read-off: familial aggregation is NECESSARY but NOT SUFFICIENT for a genetic cause - shared environment is the rival. Fig 2. 1 - Family resemblance is fed by shared genes AND shared environment. Heritability is our attempt to read off the genetic slice of the variance - but the two sources are confounded, which is exactly why we need twins. 图 2. 1 -- 家族相似性由共享基因和共享环境共同喂养。遗传力是我们试图读出方差中遗传那一份的尝试 -- 但这两个来源彼此混杂,这正是我们需要双生子的原因。 i Narrow vs broad - why we usually quote h2 狭义 vs 广义 -- 为何我们通常引用 h2 Only the additive part VA is transmitted predictably from parent to offspring and drives resemblance between relatives and response to selection. Dominance and epistasis effects are reshuffled each generation, so narrow- sense h2 is the quantity that predicts relatives' correlations - which is precisely what twin studies measure. 只有加性部分 VA 可从亲代到子代可预测地传递,并驱动亲属间的相似性和对选择的响应。显性与上位效应每代都被重新洗牌,因此狭义 h2 才是预测亲属相关的量 -- 这正是双生子研究所测量的。 - POPH90111 . Genetic Epidemiology MODULE 2 . HERITABILITY 2. 2 SD - variance: the arithmetic you will be marked on 2. 2 SD→ 方差:会被评分的算术 Almost every heritability question hands you a standard deviation or a correlation, not a variance. The single most-dropped mark is forgetting that variance = SD squared. The course also estimates everything separately by sex and by zygosity, because the spread genuinely differs between groups. 几乎每道遗传率题目给你的都是标准差或相关,而非方差。最常被丢掉的一分就是忘了方差= SD 的平方。课程还会按性别和合子性分别估计一切,因为各组间的离散度确实不同。 - EX 2A Turning a standard deviation into a variance L . variance A tutorial reports female adult height with SD = 9. 29 cm. The genetic component is estimated as VA = 55. Find Vp and then narrow-sense h2.[13]Source: asksia-bible-poph90111-bilingual.pdfOR = ad/bc。演算(ABCFS,“任一患病姐妹”):病例 13/462 对对照 1/405 → OR =(13×404)/(449×1)= 11. 7 (95% CI 1. 7-98. 2) . 3 Interpret. OR > 1 and CI excluding 1 - positive familial aggregation - "evidence for, not proof of, a Beyond the 2x2 - the other measures 超越 2×2––其他度量 SMR · RECURRENCE - RISK RATIO SMR = Observed / Expected Expected = population age/sex rates x relatives' person-time Worked: mothers of cases O=45, E=17. 7 - SMR ~ AR = risk in a type-R relative of a case / population prevalence K FRR = RR given an affected 1st-degree relative vs general pop. POPH90111 . Genetic Epidemiology genetic aetiology. " 解读。OR>1且 CI 不含1→正向家族聚集性 -- “是支持遗传性病因的证据,而非证明”。 ✓ Reading & R across degrees 跨亲缘等级解读入R AR > 1 means relatives are at raised risk. If Ap declines as relatedness falls (sib > aunt > cousin), that gradient points to a genetic contribution; the rate of decline hints at polygenic (gentle decline) vs single- gene (steep) architecture. 入R >1 意味着亲属风险升高。若入R 随亲缘关系下降而递减(同胞>姑舅>表堂亲),该梯度指向遗传贡献;递减的速率则提示是多基因(平缓递减)还是单基因(陡峭)结构。 ! Match the design to the measure 让设计与度量相匹配 OR comes from case-control; RR / rate-ratio / SMR come from cohort designs. Quoting an RR off a case- control table (where you can't estimate risk) is a classic appraisal slip. And always close with the mantra: aggregation is evidence for, not proof of, an inherited aetiology. OR 来自病例对照;RR/ 率比 / SMR 来自队列设计。从一张病例对照表(你无法估计风险)上引用 RR 是典型的评价失误。并且始终以那句口诀收尾:聚集性是支持遗传性病因的证据,而非证明。 POPH90111 . Genetic Epidemiology MODULE 2 . HERITABILITY UNDERSTAND . LO3 MODULE 2 . HERITABILITY How much of the variation is genetic? 变异中有多少源于遗传 Variance components . twin studies . Falconer . ACE . liability threshold 方差成分 · 双生子研究 · Falconer · ACE · 易感性阈值 Familial aggregation told us a trait runs in families. Heritability asks the sharper, quantitative question: of all the variation we see in a trait across a population, what proportion is due to genetic differences between people? The answer is a number between 0 and 1 - and the whole module is the machinery for estimating it, almost entirely from twins. This is the most calculation-heavy stretch of the course: you will partition variance, run Falconer's formula, solve the ACE equations, and map a yes/no disease onto a hidden continuous liability. Every estimate comes wrapped in the same critical-appraisal caution - heritability is a property of a population in an environment, never of an individual. 家族聚集性告诉我们某性状在家庭中流传。遗传率则提出更尖锐的定量问题:在一个人群中所见某性状的全部变异里,有多大比例归因于人与人之间的遗传差异?答案是一个介于0与1之间的数字 -- 而整个模块就是估计它的机器,且几乎完全依靠双生子。这是全课程计算量最大的一段:你将分解方差、运用 Falconer 公式、求解 ACE 方程组,并把一个是/否的疾病映射到一个隐藏的连续易感性上。每个估计都裹挟着同一句批判性评价告诫 -- 遗传率是某一环境中某一人群的属性,绝非个体的属性。

Twin study basics：MZ 共享约 100% 基因、DZ 约 50%；比较 MZ 与 DZ 的相关/一致率来分离基因与环境影响。[30]Source: asksia-cheatsheet-poph90111.pdf8b . Family Designs M1 EXTRAS Case-control-family / case-family: relatives directly interviewed = OR / RR / SMR; relatives of controls are hard to recruit, and the case-family design needs a population registry. Outcome can be analysed as dichotomous (affected y/n), ordinal (number affected) or multinomial - match the analysis to how family history was coded. 9 . Heritability MODULE 2 = proportion of phenotypic variance due to genetic variance. A property of a population in an environment, not an individual. Variance = SD2 (e. g. height SD 9. 29 => variance = 86). VARIANCE PARTITION Vp = Vg + Ve Vg = Va + Vd (+ Vi) Broad-sense H2 = Vg/Vp Narrow-sense h2 = Va/Vp (h2 ≤ H2) Narrow-sense (additive Va) predicts relative resemblance & response to selection; Vd = dominance, Vi = epistatic/interaction variance. Estimate variance separately by sex & zygosity (M>F; DZ>MZ spread). 10 . Twin Studies THE ENGINE MZ share ~100% genes; DZ ~50% (like full sibs). Both share rearing env -> comparing them isolates genetics; twins control for age & shared env. Binary: concordance = proportion of pairs both affected; conc_MZ > conc_DZ => genetic . Continuous: correlate twin-1 vs twin-2. FALCONER'S HERITABILITY h2 = 2 (r_MZ - r_DZ) (continuous) Worked: h2 = 2 (conc_MZ - conc_DZ) (binary) Worked: female height r_MZ=0. 78, r_DZ=0. 46 = h2 = 2(0. 78-0. 46) = 0. 64 - 64% of variance in female height is additively genetic. Interpret: "consistent with, but not proof of, an inherited genetic aetiology. " Genetic variance from heritability: Vg = h2 x Vp. With Vp=86 and h2=0. 64 => Vg=55. Opposite-sex DZ pairs & the twin-co-twin (TRA) design extend the model to probe shared-environment and sex effects. 11 . ACE Model VARIANCE COMPONENTS Split Vp into A additive genetic, C common/shared env, E unique env + error. From twin correlations: ACE FROM R_MZ, R_DZ r_MZ = A + C . r_DZ = %A + C A = 2(r_MZ - r_DZ) (= Falconer) C = 2. r_DZ - r_MZ . E = 1 - r_MZ Worked: r_MZ=0. 78, r_DZ=0. 46 => A=2(0. 78-0. 46)=0. 64; C=2(0. 46)-0. 78=0. 14; E=1-0. 78=0. 22. Check: A+C+E = 0. 64+0. 14+0. 22 = 1. 00 V. So C is the part of resemblance shared equally by both twin types; E (incl. measurement error) is the only thing that makes MZ co-twins differ. Trap - equal- environments assumption: if MZ pairs are treated more alike than DZ, shared env masquerades as genes = h2 overestimated . 4 11b . Classic Twin Model ASSUMPTIONS · Random mating (no assortative mating inflating r_DZ) Concordance/correlation are estimated separately by sex & zygosity because variance differs. Binary worked: conc_MZ=0. 40, conc_DZ=0. 15 => h2(liability) = 2(0. 40-0. 15) = 0. 50 . MZ>DZ concordance is the signal; near-equality (conc_MZ=conc_DZ) => shared environment, not genes, drives the resemblance. Compiled by AskSia . mapped to the POPH90111 syllabus . asksia. ai/cheatsheet/unimelb-poph90111 12 . Liability- Threshold BINARY TRAITS

USE IN PRACTICE（M8，筛查）

Sensitivity/Specificity：检验固有属性；PPV/NPV 依赖患病率。[6]Source: asksia-bible-poph90111-bilingual.pdf— Cases only; under GLE in the source population, a G-E association among cases efficiently estimates the multiplicative interaction (biased if G,E correlated). Module 8 - Screening (USE IN PRACTICE) Wilson-Jungner principles — WHO (1968) 10-point checklist: important condition with a latent stage & understood natural history, a suitable acceptable test, an accepted action, balanced cost. Number needed to treat (NNT) — NNT = 1/ Absolute Risk Reduction, with ARR = carrier risk x proportion risk reduced by treatment; carriers treated to prevent one case. POPH90111 . Genetic Epidemiology Term (EN) 中文 One-line meaning Number needed to screen (NNS) — NNS = NNT / carrier frequency; people screened to prevent one case - collapses for rare variants, so genetic screening is targeted. Absolute risk reduction (ARR) — The drop in absolute risk from the action: ARR = baseline risk - treated risk; the reciprocal of NNT. Sensitivity TP/(TP+FN) = P(test+ | diseased); the test's ability to detect true cases. An intrinsic test — property. Specificity — TN/(TN+FP) = P(test- | healthy); correctly clears the well. An intrinsic test property. PPV / NPV — PPV = TP/(TP+FP) = P(diseased | test+); NPV = TN/(TN+FN); PPV rises and NPV falls as prevalence rises - why low-prevalence screens give many false positives. ROC curve / AUC — Sensitivity vs 1-specificity across cut-offs; AUC = P(a random case scores above a random control); 0. 5 = chance, 1. 0 = perfect (CAD PRS AUC ~ 0. 81). ★ How to drill this glossary Az 如何演练这份术语表用法 Three layers per term: recall the term from the meaning, recall the formula where one exists, and say the one-line appraisal hook (e. g. "aggregation is evidence for, not proof of, a genetic cause"; "PPV depends on prevalence"). The exam and assignments reward the hook as much as the number. 〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕每个术语三层:由释义回忆术语、回忆公式(若存在)、复述那句一行评价钩子(如“聚集性是支持遗传原因的证据,而非证明”;“PPV取决于患病率”)。考试和作业奖励钩子的程度不亚于数字。〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕 POPH90111 . Genetic Epidemiology PRACTICE Q1-Q2 [2]Source: asksia-bible-poph90111-bilingual.pdf! Critical appraisal - a good test can still be useless for screening 批判性评价 -- 再好的检验也可能不适合筛查 Sensitivity and specificity are intrinsic, but PPV depends on prevalence. A test with excellent sensitivity/specificity can be near-useless in a low-prevalence general population (PPV near zero) - exactly why genetic screening targets high-prior-risk groups. The ROC/AUC summarises discrimination across cut-offs; moving the cut-off trades sensitivity against specificity but never changes prevalence. 灵敏度和特异度是内在的,但PPV 取决于患病率。一个灵敏度/特异度极佳的检验,在低患病率的一般人群中可能近乎无用(PPV 接近零) -- 这正是遗传筛查靶向高先验风险人群的原因。ROC/AUC 概括跨切点的区分度;移动切点是在灵敏度与特异度之间权衡,但从不改变患病率。 Same habit on every item: calculate, interpret, appraise. The number alone is a fraction of the marks - the interpretation sentence and the design critique (bias, assumption, scale, prevalence) are where POPH90111 assessment lives. Write the appraisal sentence even when the question only asks for the number. 每道题都保持同一习惯:计算、解读、评价。光有数字只占一小部分分数 -- 解读句和设计批判(偏倚、假设、尺度、患病率)才是 POPH90111 评估的所在。即便题目只问数字,也写出那句评价。 MARKER'S NOTE . POPH90111 . CALCULATE + INTERPRET + APPRAISE POPH90111 . Genetic Epidemiology AskSia Library VISUAL STUDY BIBLE . ASKSIA POP. & GLOBAL HEALTH SEMESTER 1 . 2026 p < 5x10-8 - THE COMPLETE STUDY BIBLE - Genetic Epidemiology 遗传流行病学 FROM A DNA STRAND TO A GWAS SKYLINE - PLUG THE NUMBERS AND JUDGE THE STUDY DESIGN. 墨尔本大学 POPH90111 · 双语视觉精读 · 在线开卷作业占 90% · 遗传率/GWAS/孟德尔随机化/ 筛查:计算 + 研究设计评价工具箱 POPH90111 . UNIVERSITY OF MELBOURNE 中英双语版 · BILINGUAL EDITION 英文主讲,中文随行一考试要点与术语保留英文原词 There is no closed-book exam in this subject. Your whole mark is three take-home pieces - a 10% online MCQ and two written assignments worth 90% combined - and all three are built from the same three task types: calculate, interpret, and critically appraise the study design. This book is therefore a calculation + appraisal toolkit: every method shown on real course numbers, every design tagged with its signature bias. Independent study companion. Not affiliated with or endorsed by the University of Melbourne. Corrections: takedowns@asksia. ai PREFACE - HOW TO USE THIS BOOK Plug the numbers, judge the design 代入数字,评判设计 Open-book and take-home - so it tests whether you can DO the method and APPRAISE it 开卷且带回家作答,因此考的是你能否动手做方法并加以评价 This is not a transcript of the lecture slides. It is a self-contained toolkit for every quantity and every study design POPH90111 examines - each concept opens with a diagram, states the formula plainly, works it on the course's own example numbers, gives a memorable analogy, then flags the assignment trap. Because all three assessments are open-book and take-home, the examiner cannot reward what you merely remember. Marks come from three things only: can you calculate it, can you interpret the output, and can you critically appraise the design that produced it? - - 这不是讲座幻灯片的逐字稿,而是一份自足的工具箱,涵盖 POPH90111 所考的每个量和每种研究设计 -- 每个概念都以一幅图开篇,明白地写出公式,用课程自带的例题数字加以演算,给出一个易记的类比,再标出作业陷阱。由于三项评估全部开卷且带回家作答,考官无法奖励你单纯记住的东西。分数仅来自三件事:你能否算出它、能否解释输出、能否批判性地评价产生它的设计?

NNT/NNS：用 ARR 与 carrier frequency 把“是否值得筛查”量化；遗传筛查倾向于瞄准高风险人群。[6]Source: asksia-bible-poph90111-bilingual.pdf— Cases only; under GLE in the source population, a G-E association among cases efficiently estimates the multiplicative interaction (biased if G,E correlated). Module 8 - Screening (USE IN PRACTICE) Wilson-Jungner principles — WHO (1968) 10-point checklist: important condition with a latent stage & understood natural history, a suitable acceptable test, an accepted action, balanced cost. Number needed to treat (NNT) — NNT = 1/ Absolute Risk Reduction, with ARR = carrier risk x proportion risk reduced by treatment; carriers treated to prevent one case. POPH90111 . Genetic Epidemiology Term (EN) 中文 One-line meaning Number needed to screen (NNS) — NNS = NNT / carrier frequency; people screened to prevent one case - collapses for rare variants, so genetic screening is targeted. Absolute risk reduction (ARR) — The drop in absolute risk from the action: ARR = baseline risk - treated risk; the reciprocal of NNT. Sensitivity TP/(TP+FN) = P(test+ | diseased); the test's ability to detect true cases. An intrinsic test — property. Specificity — TN/(TN+FP) = P(test- | healthy); correctly clears the well. An intrinsic test property. PPV / NPV — PPV = TP/(TP+FP) = P(diseased | test+); NPV = TN/(TN+FN); PPV rises and NPV falls as prevalence rises - why low-prevalence screens give many false positives. ROC curve / AUC — Sensitivity vs 1-specificity across cut-offs; AUC = P(a random case scores above a random control); 0. 5 = chance, 1. 0 = perfect (CAD PRS AUC ~ 0. 81). ★ How to drill this glossary Az 如何演练这份术语表用法 Three layers per term: recall the term from the meaning, recall the formula where one exists, and say the one-line appraisal hook (e. g. "aggregation is evidence for, not proof of, a genetic cause"; "PPV depends on prevalence"). The exam and assignments reward the hook as much as the number. 〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕每个术语三层:由释义回忆术语、回忆公式(若存在)、复述那句一行评价钩子(如“聚集性是支持遗传原因的证据,而非证明”;“PPV取决于患病率”)。考试和作业奖励钩子的程度不亚于数字。〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕 POPH90111 . Genetic Epidemiology PRACTICE Q1-Q2 [11]Source: asksia-bible-poph90111-bilingual.pdfNNS - HIGH FAMILY HISTORY NNS -- 高家族史 ✓ Analogy - the lottery-ticket cost 类比 -- 彩票的代价 NNT is the price of a winning ticket once you are in the right queue (a carrier). NNS is the price including finding the right queue: in the general population you sift ~150 people to find one carrier, so the cost per prevented case balloons. Walk into a queue already full of carriers (high family history) and the sifting cost collapses. NNT 是当你已身处正确队列(即一名携带者)时一张中奖彩票的价格。NNS 则是加上找到正确队列的价格:在一般人群中你要筛过约150人才能找到一名携带者,于是每避免一例的成本暴涨。走进一个已挤满携带者的队列(高家族史),筛选成本就崩塌。 POPH90111 . Genetic Epidemiology ! Exam trap - NNS collapses for rare variants 考试陷阱 -- NNS 对罕见变异会失效 Screening efficiency (NNS) is dominated by carrier frequency, not by how good the treatment is. A wonderful treatment (low NNT) is wasted if you must screen thousands to find one carrier. Raising the prior probability of carriage - targeting high-family-history groups - is what makes a genetic screen worthwhile. State NNT and NNS, and always name the population the carrier frequency refers to. 筛查效率(NNS)由携带者频率主导,而非由治疗有多好主导。一个再好的治疗(低 NNT)若你必须筛上千人才找到一名携带者,也是浪费。提高携带的先验概率 -- 靶向高家族史人群 -- 才是让一项遗传筛查值得做的关键。陈述 NNT 和 NNS,并始终点名携带者频率所指的人群。 POPH90111 . Genetic Epidemiology M8 . TEST METRICS - - MODULE 8 . EVALUATING A TEST STANDARD CANON Sensitivity, specificity, PPV / NPV 灵敏度、特异度、PPV / NPV The 2×2 of test result x true status - and why PPV depends on prevalence 检验结果 × 真实状态的 2×2 表 -- 以及 PPV 为何取决于患病率 Any "evaluate this test" question reduces to a 2×2 of test result (+/-) against true disease status (D+/D-), giving TP, FP, FN, TN. From it come four metrics - two intrinsic to the test (sensitivity, specificity) and two that depend on who you test (PPV, NPV). 任何“评价这项检验”的问题都归结为一张 2×2 表,列出检验结果(+/-)与真实疾病状态 (D+/D-),给出 TP、FP、FN、 TN。由它得出四项指标 -- 两项是检验固有的(灵敏度、特异度),两项取决于你检测的是谁(PPV、NPV)。 D5 machinery used for screening: read TP / FP / FN / TN off the cells. (Here the row split is test +/-, the column split i Disease: YES Disease: NO Exposed / FamHx + a b OR = (a x d) / (b xc) Unexposed / FamHx - C d RR = [a/(a+b)] / [c/(c+d)][20]Source: asksia-cheatsheet-poph90111.pdfSIA > Show the working: in this subject the marks live in the setup and the interpretation, not the final digit. Always write the formula, the substitution, then one sentence of meaning. asksia. ai/cheatsheet/ unimelb-poph90111 . side 2/2 AskSia CHEATSHEET SERIES Disease screening = a systematic test to find asymptomatic disease/precursors in people not seeking care. Genetic screening = find risk-raising variants in asymptomatic people so risk can be reduced/prevented; can be population-wide but is usually targeted to high-prior-risk groups (e. g. strong family history). Course twist: a genetic test can be "once-and-for-all" (your germline doesn't change), unlike repeated disease screening. Two uses: screen for genetic risk, or use a genetic factor to screen for disease. 30 . Wilson-Jungner WHO 1968 The screening-evaluation checklist (the course adapts all 10 to genetics): · Facilities for diagnosis & treatment exist Trap: "we can test" # "we should screen. " A test only helps if knowing the result reduces disease/disability/death and benefits beat harms (psychological, social, insurance, variants of unknown significance, false positives). Example genes the course uses: BRCA1/2, the mismatch-repair (MMR) genes, HTT - note HTT (Huntington) has no risk-reduction, which weakens the case for screening. 31 . NNT & NNS QUANTIFY BENEFIT ARR = carrier risk x proportion risk reduced NNT = 1 / ARR NNS = NNT / carrier frequency Worked (BRCA1/2): carrier breast-cancer risk to 70 = 0. 4; tamoxifen cuts risk 50% => ARR = 0. 4×0. 5 = 0. 2 => NNT = 1/0. 2 = 5 carriers treated to prevent one cancer. Carrier freq 0. 0067 (1 in 150) = NNS = 5/0. 0067 = 746 screened per cancer prevented. High-FH group (carrier freq 0. 25) = NNS = 5/0. 25 = 20 - far more efficient => justifies targeted screening. CARRIER FREQ NNT NNS 0. 0067 (general) =746 0. 05 (moderate FH) 0. 25 (strong FH)

Wilson–Jungner（WHO 1968）原则：筛查要满足疾病重要、有潜伏期/自然史清楚、检验合适可接受、后续行动有效等；“能测 ≠ 该筛”。[6]Source: asksia-bible-poph90111-bilingual.pdf— Cases only; under GLE in the source population, a G-E association among cases efficiently estimates the multiplicative interaction (biased if G,E correlated). Module 8 - Screening (USE IN PRACTICE) Wilson-Jungner principles — WHO (1968) 10-point checklist: important condition with a latent stage & understood natural history, a suitable acceptable test, an accepted action, balanced cost. Number needed to treat (NNT) — NNT = 1/ Absolute Risk Reduction, with ARR = carrier risk x proportion risk reduced by treatment; carriers treated to prevent one case. POPH90111 . Genetic Epidemiology Term (EN) 中文 One-line meaning Number needed to screen (NNS) — NNS = NNT / carrier frequency; people screened to prevent one case - collapses for rare variants, so genetic screening is targeted. Absolute risk reduction (ARR) — The drop in absolute risk from the action: ARR = baseline risk - treated risk; the reciprocal of NNT. Sensitivity TP/(TP+FN) = P(test+ | diseased); the test's ability to detect true cases. An intrinsic test — property. Specificity — TN/(TN+FP) = P(test- | healthy); correctly clears the well. An intrinsic test property. PPV / NPV — PPV = TP/(TP+FP) = P(diseased | test+); NPV = TN/(TN+FN); PPV rises and NPV falls as prevalence rises - why low-prevalence screens give many false positives. ROC curve / AUC — Sensitivity vs 1-specificity across cut-offs; AUC = P(a random case scores above a random control); 0. 5 = chance, 1. 0 = perfect (CAD PRS AUC ~ 0. 81). ★ How to drill this glossary Az 如何演练这份术语表用法 Three layers per term: recall the term from the meaning, recall the formula where one exists, and say the one-line appraisal hook (e. g. "aggregation is evidence for, not proof of, a genetic cause"; "PPV depends on prevalence"). The exam and assignments reward the hook as much as the number. 〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕每个术语三层:由释义回忆术语、回忆公式(若存在)、复述那句一行评价钩子(如“聚集性是支持遗传原因的证据,而非证明”;“PPV取决于患病率”)。考试和作业奖励钩子的程度不亚于数字。〔每个术语三层:由释义回忆术语、回忆公式、复述那句批判性结论。〕 POPH90111 . Genetic Epidemiology PRACTICE Q1-Q2 [20]Source: asksia-cheatsheet-poph90111.pdfSIA > Show the working: in this subject the marks live in the setup and the interpretation, not the final digit. Always write the formula, the substitution, then one sentence of meaning. asksia. ai/cheatsheet/ unimelb-poph90111 . side 2/2 AskSia CHEATSHEET SERIES Disease screening = a systematic test to find asymptomatic disease/precursors in people not seeking care. Genetic screening = find risk-raising variants in asymptomatic people so risk can be reduced/prevented; can be population-wide but is usually targeted to high-prior-risk groups (e. g. strong family history). Course twist: a genetic test can be "once-and-for-all" (your germline doesn't change), unlike repeated disease screening. Two uses: screen for genetic risk, or use a genetic factor to screen for disease. 30 . Wilson-Jungner WHO 1968 The screening-evaluation checklist (the course adapts all 10 to genetics): · Facilities for diagnosis & treatment exist Trap: "we can test" # "we should screen. " A test only helps if knowing the result reduces disease/disability/death and benefits beat harms (psychological, social, insurance, variants of unknown significance, false positives). Example genes the course uses: BRCA1/2, the mismatch-repair (MMR) genes, HTT - note HTT (Huntington) has no risk-reduction, which weakens the case for screening. 31 . NNT & NNS QUANTIFY BENEFIT ARR = carrier risk x proportion risk reduced NNT = 1 / ARR NNS = NNT / carrier frequency Worked (BRCA1/2): carrier breast-cancer risk to 70 = 0. 4; tamoxifen cuts risk 50% => ARR = 0. 4×0. 5 = 0. 2 => NNT = 1/0. 2 = 5 carriers treated to prevent one cancer. Carrier freq 0. 0067 (1 in 150) = NNS = 5/0. 0067 = 746 screened per cancer prevented. High-FH group (carrier freq 0. 25) = NNS = 5/0. 25 = 20 - far more efficient => justifies targeted screening. CARRIER FREQ NNT NNS 0. 0067 (general) =746 0. 05 (moderate FH) 0. 25 (strong FH)

POPH90111

0）先把“考试/评分结构”搞清楚（决定你该怎么复习）

1）整门课的“高频得分链条”（你要练到闭眼能写）

链条 A：家族聚集性（Familial aggregation）——2×2 → OR/RR/SMR → 经典评价句

链条 B：遗传率（Heritability）——方差分解 → Falconer $h^2$ → ACE → 评价“等环境假设”

链条 C：检验/筛查指标（Sensitivity/Specificity/PPV/NPV）——2×2 → 指标 → 评价“患病率/先验概率”

链条 D：ROC / AUC（区分度）——“能分开” ≠ “有用”

链条 E：NNT / NNS（筛查是否“划算”的数字证据）——ARR → NNT → NNS → “靶向高风险”

链条 F：关键“通用评价框架”（LO5）——设计 → 度量 → 优势 → 局限 → 偏倚方向

2）你“必须背熟”的核心术语/定义清单（按模块流水线）

UNDERSTAND（M1–M2）

USE IN PRACTICE（M8，筛查）

3）最常见“扣分陷阱清单”（考前必刷）

4）给你一个“最后 48 小时冲刺计划”（按最省命的顺序）

5）你告诉我 2 个信息，我就能把这份“复习重点”继续细化到你这次 final/作业的题型清单

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