Contribution of a genetic risk score to ethnic differences in fatty liver disease.
Contribution of a genetic risk score to ethnic differences in fatty liver disease.
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DOI：
10.1111/liv.15322
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发表时间：
2022-10
影响因子：
6.7
通讯作者：
Kozlitina, Julia
中科院分区：
文献类型：
--
作者：
Kubiliun, Maddie J.;Cohen, Jonathan C.;Hobbs, Helen H.;Kozlitina, Julia
关键词：
脂肪肝（FLD）的易感性在个体之间和种族/民族之间存在差异。一些遗传变异影响FLD风险，但这些变异是否解释了FLD患病率的种族/民族差异尚不清楚。我们研究了遗传危险因素对FLD种族/民族特异性差异的贡献。进行了一项病例对照研究，比较了FLD患者（n = 1194）和基于人群的对照（n = 3120）。检查患者特征、FLD风险变体（PNPLA3-rs738409 + rs6006460、TM6SF2-rs58542926、HSD17 B13-rs80182459 + rs72613567、MBOAT7/TMC 4-rs641738和GCKR-rs1260326）和多位点遗传风险评分（GRS）。确定了具有不同危险因素负担的个体发生FLD的几率。与选择对照的人群相比，在FLD患者中，西班牙裔和白人的比例过高（分别为56%和36%和29%），黑人的比例偏低（5%和23%）（p <0.001）。在病例组和对照组中，与白人相比，黑人的风险等位基因净数量较低，而西班牙裔的风险等位基因净数量较高（p <0.001）。GRS与FLD几率增加相关（ORQ5vsQ1 = 8.72 [95%CI = 5.97 - 13.0]，p = 9.8 × 10 − 28），西班牙裔的相关性（ORQ5vsQ1 = 14.8 [8.3 - 27.1]）强于黑人（ORQ5vsQ1 = 3.7 [1.5 - 11.5]，P-相互作用= 0.002）。在考虑GRS后，西班牙裔和白人之间的FLD几率没有显著差异（OR = 1.06 [0.87 - 1.28]，p = 0.58），而黑人的FLD几率要低得多（OR = 0.21，[0.15 - 0.30]，p <0.001）。与白人相比，黑人有较低的FLD风险等位基因负担，而西班牙裔有较大的FLD风险等位基因负担。这些差异促成了但不能完全解释FLD患病率的种族/民族差异。识别保护黑人免于FLD的其他因素可能为FLD的预防和治疗提供新的靶点。
Susceptibility to fatty liver disease (FLD) varies among individuals and between racial/ethnic groups. Several genetic variants influence FLD risk, but whether these variants explain racial/ethnic differences in FLD prevalence is unclear. We examined the contribution of genetic risk factors to racial/ethnic-specific differences in FLD. A case–control study comparing FLD patients (n = 1194) and population-based controls (n = 3120) was performed. Patient characteristics, FLD risk variants (PNPLA3-rs738409 + rs6006460, TM6SF2-rs58542926, HSD17B13-rs80182459 + rs72613567, MBOAT7/TMC4-rs641738, and GCKR-rs1260326) and a multi-locus genetic risk score (GRS) were examined. The odds of FLD for individuals with different risk factor burdens were determined. Hispanics and Whites were over-represented (56% vs. 38% and 36% vs. 29% respectively) and Blacks under-represented (5% vs. 23%) among FLD patients, compared to the population from which controls were selected (p < .001). Among cases and controls, Blacks had a lower and Hispanics a greater, net number of risk alleles than Whites (p < .001). GRS was associated with increase odds of FLD (ORQ5vsQ1 = 8.72 [95% CI = 5.97–13.0], p = 9.8 × 10−28), with the association being stronger in Hispanics (ORQ5vsQ1 = 14.8 [8.3–27.1]) than Blacks (ORQ5vsQ1 = 3.7 [1.5–11.5], P-interaction = 0.002). After accounting for GRS, the odds of FLD between Hispanics and Whites did not differ significantly (OR = 1.06 [0.87–1.28], p = .58), whereas Blacks retained much lower odds of FLD (OR = 0.21, [0.15–0.30], p < .001). Blacks had a lower and Hispanics a greater FLD risk allele burden than Whites. These differences contributed to, but did not fully explain, racial/ethnic differences in FLD prevalence. Identification of additional factors protecting Blacks from FLD may provide new targets for prevention and treatment of FLD.
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影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
29.4
作者：
Mancina RM;Dongiovanni P;Petta S;Pingitore P;Meroni M;Rametta R;Borén J;Montalcini T;Pujia A;Wiklund O;Hindy G;Spagnuolo R;Motta BM;Pipitone RM;Craxì A;Fargion S;Nobili V;Käkelä P;Kärjä V;Männistö V;Pihlajamäki J;Reilly DF;Castro-Perez J;Kozlitina J;Valenti L;Romeo S
通讯作者：
Romeo S
影响因子：
11.1
作者：
Dongiovanni P;Stender S;Pietrelli A;Mancina RM;Cespiati A;Petta S;Pelusi S;Pingitore P;Badiali S;Maggioni M;Mannisto V;Grimaudo S;Pipitone RM;Pihlajamaki J;Craxi A;Taube M;Carlsson LMS;Fargion S;Romeo S;Kozlitina J;Valenti L
通讯作者：
Valenti L
影响因子：
3.6
作者：
Gao F;Zheng KI;Chen SD;Lee DH;Wu XX;Wang XD;Targher G;Byrne CD;Chen YP;Kim W;Zheng MH
通讯作者：
Zheng MH
影响因子：
3.2
作者：
Levy, Robert E.;Catana, Andreea M.;Medici, Valentina
通讯作者：
Medici, Valentina