Non-canonical open reading frames (ORFs) 非經(jīng)典的開放閱讀框

the ~20,000 canonical, well-annotated genes 兩萬個經(jīng)典的注釋良好的基因

ribosome-associated RNAs 核糖體相關(guān)的RNA

inflammatory bowel disease 炎癥性腸病 comorbidity 合并癥

chronic disorders 慢性疾病 common pathophysiological processes 常見的病理生理過程

the BioMe BioBank?是一個與電子病歷相關(guān)的生物庫忧勿，使研究人員能夠快速有效地進行遺傳褂策、流行病學(xué)、分子等方面的研究

Optimal Unified Approach 最優(yōu)統(tǒng)一方法

burden test 負荷測試?same direction 相同方向

sequence kernel association test 序列核關(guān)聯(lián)測試?different direction 不同方向?nonburden tests 非負荷測試?kernel matrix 核矩陣?SNP-SNP interactions?SNP-SNP 相互作用?

dichotomous 二分法 acute-lung-injury 急性肺損傷 etiology 病因?qū)W?implicitly?隱含地?magnitudes 程度

Single-variant tests 單變異測試

rare-variant effects 罕見變異效應(yīng)?low frequencies 低頻?large numbers 數(shù)目多?cumulative effects 累積效應(yīng)

the cohort allelic sum test 隊列等位基因總和檢驗 weighted sum test (WST)?加權(quán)和檢驗?

substantial 重大的?attractive power 吸引力?adipose cells? 脂肪細胞

SKAT-O automatically behaves like the burden test when the burden test is more powerful than SKAT, and behaves like SKAT when the SKAT is more powerful than the burden test.?當(dāng)負荷測試比 SKAT 更強大時，SKAT-O 自動表現(xiàn)得像負荷測試哼勇，而當(dāng) SKAT 比負荷測試更強大時烟零，SKAT-O 會自動表現(xiàn)得像 SKAT醉锄。

kurtosis 峰度?subjects 主題?asymptotically 漸近地?notation 符號?foregoing 前面的?substantial interest 重大利益?elucidate 闡明?leptin, a hormone that regulates appetite 瘦素偿曙，調(diào)控食欲?

the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP)?美國國家心肺血液研究所外顯子組測序項目

the acute lung injury (ALI) exome-sequencing data?急性肺損傷 (ALI) 外顯子組測序數(shù)據(jù)

the chronic Pseudomonas aeruginosa infection?慢性銅綠假單胞菌感染

SKAT-O 優(yōu)于 SKAT 和 burden test

additive genetic model 加性遺傳模型?reduce the df and increase analysis power 降低自由度并提高分析能力?

SKAT is a variance-component test under the induced logistic mixed model?SKAT是歸納邏輯混合模型下的方差分量檢驗

n×n kernel matrix；核矩陣谜洽；n×m genotype matrix萝映；基因型矩陣；m×m diagonal weight matrix阐虚；對角權(quán)重矩陣

the trait is binary and sample sizes are small, e.g., hundreds of subjects,? 性狀為二分類并且樣本量為幾百個時序臂，lead to incorrect type I error control and power loss. I類錯誤率不正常并且喪失效能

small-sample-adjusted p value calculations for SKAT and SKAT-O 兩種方式都有小樣本量校正的p值

asymptotic null distribution?漸近零分布?the calibrated coalescent model?校準的聚結(jié)模型

N, Beta(1, 25) weights 權(quán)重；equal-sized grids 等大小的網(wǎng)格

Note that α = 2.5×10 ? 6 is Bonferroni-adjusted level α = 0.05 when simultaneously testing 20,000 genes.

圖：Manhattan plots of common- and rare-variant associations for T2D实束，第一張圖GWAS results for common variants (MAF?≥?0.01) 贸宏，第二張圖GWAS results of rare variants (0.0001?≤?MAF?<?0.01) in UKB，

【2020 Nature磕洪；Identification of type 2 diabetes loci in 433,540 East Asian individuals】Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals (effective sample size, Neff = 211,793).?we identified 301 distinct association signals at 183 loci.?we identified 61 loci that are newly implicated in predisposition to T2D.?We defined ‘lead’ variants as the strongest T2D-associated variants with P < 5 × 10?8 and defined the region ±500 kb from the lead variant as a locus.?我們將“先導(dǎo)”變體定義為 P < 5 × 10?8 的最強 T2D 相關(guān)變體吭练，并將先導(dǎo)變體 ±500 kb 的區(qū)域定義為基因座。A locus was considered ‘novel’ if the lead variant was located at least 500 kb from previously reported T2D-associated variants in any ancestry.?如果先導(dǎo)變異位于任何祖先中與之前報道的 T2D 相關(guān)變異至少 500 kb 的位置析显，則該位點被認為是“新穎的”鲫咽。we identified lead variants associated with T2D at 183 loci, of which 51 were novel.?我們在 183 個位點鑒定了與 T2D 相關(guān)的先導(dǎo)變異，其中 51 個是新的谷异。Lead variants at all novel loci were common (minor allele frequency (MAF) ≥ 5%)分尸。所有新位點的先導(dǎo)變異都很常見（次要等位基因頻率 (MAF) ≥ 5%）。Using genome-wide complex trait analysis (GCTA), we identified 301 distinct association signals that met a locus-wide significance threshold of P < 1 × 10?5, 228 of which were genome-wide significant (P < 5 × 10?8). 使用全基因組復(fù)雜性狀分析 (GCTA)歹嘹，我們確定了 301 個不同的關(guān)聯(lián)信號箩绍，這些信號滿足 P < 1 × 10?5 的全基因座顯著性閾值，其中 228 個具有全基因組顯著性 (P < 5 × 10?8)尺上。Overall, we observed 2–4 signals at 46 loci and 5 or more signals at 12 loci.?總體而言材蛛，我們在 46 個位點觀察到 2-4 個信號圆到，在 12 個位點觀察到 5 個或更多信號。