Autozygosity influences cardiometabolic disease-associated traits in the AWI-Gen sub-Saharan African study.
Autozygosity influences cardiometabolic disease-associated traits in the AWI-Gen sub-Saharan African study.
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DOI：
10.1038/s41467-020-19595-y
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发表时间：
2020-11-13
影响因子：
16.6
通讯作者：
Ramsay M
中科院分区：
文献类型：
--
作者：
Ceballos FC;Hazelhurst S;Clark DW;Agongo G;Asiki G;Boua PR;Xavier Gómez-Olivé F;Mashinya F;Norris S;Wilson JF;Ramsay M
对自合性效应的分析揭示了定向显性或超显性的存在。自合性效应是指遗传亲缘后代中一个性状的平均值的变化。在这项研究中，我们使用从加纳、布基纳法索、肯尼亚和南非招募的10,000多名撒哈拉以南非洲人的数据，在13个心脏代谢疾病相关性状中检测到4个自合子效应的证据。研究发现，自合性对这些表型的影响与性别有关，近亲交配对男性的影响显著降低，但对女性的几个特征(体重指数、皮下脂肪组织、低密度脂蛋白和总胆固醇水平)的影响显著增加。总体而言，近亲繁殖抑郁对男性的影响更大。不同夜光强度的研究地点之间也观察到近亲繁殖抑制的不同影响，作为城市发展的代表。这些结果表明，在非洲Wits-INDEPTH基因组研究伙伴关系(AWI-GEN)队列中，这些性状的定向显性遗传成分是由环境交互作用和性别特有的遗传结构差异介导的。在整个非洲，心脏代谢性疾病(CMD)的患病率正在迅速增加。在这里，作者调查了10,000多名撒哈拉以南非洲人的CMD相关性状的自合性，表明这些性状受到特定性别的近亲繁殖抑郁和环境相互作用的影响。
The analysis of the effects of autozygosity, measured as the change of the mean value of a trait among offspring of genetic relatives, reveals the existence of directional dominance or overdominance. In this study we detect evidence of the effect of autozygosity in 4 out of 13 cardiometabolic disease-associated traits using data from more than 10,000 sub-Saharan African individuals recruited from Ghana, Burkina Faso, Kenya and South Africa. The effect of autozygosity on these phenotypes is found to be sex-related, with inbreeding having a significant decreasing effect in men but a significant increasing effect in women for several traits (body mass index, subcutaneous adipose tissue, low-density lipoproteins and total cholesterol levels). Overall, the effect of inbreeding depression is more intense in men. Differential effects of inbreeding depression are also observed between study sites with different night-light intensity used as proxy for urban development. These results suggest a directional dominant genetic component mediated by environmental interactions and sex-specific differences in genetic architecture for these traits in the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen) cohort. The prevalence of cardiometabolic diseases (CMDs) is increasing rapidly across Africa. Here, the authors investigate autozygosity in CMD-associated traits in over 10,000 sub-Saharan African individuals, showing these traits are influenced by sex-specific inbreeding depression and environmental interactions.
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影响因子：
3.7
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
通讯作者：
Butte NF
影响因子：
3.7
作者：
Bruederle A;Hodler R
通讯作者：
Hodler R
影响因子：
3.7
作者：
Alvarez, Gonzalo;Ceballos, Francisco C.;Quinteiro, Celsa
通讯作者：
Quinteiro, Celsa
影响因子：
64.8
作者：
Joshi PK;Esko T;Mattsson H;Eklund N;Gandin I;Nutile T;Jackson AU;Schurmann C;Smith AV;Zhang W;Okada Y;Stančáková A;Faul JD;Zhao W;Bartz TM;Concas MP;Franceschini N;Enroth S;Vitart V;Trompet S;Guo X;Chasman DI;O'Connel JR;Corre T;Nongmaithem SS;Chen Y;Mangino M;Ruggiero D;Traglia M;Farmaki AE;Kacprowski T;Bjonnes A;van der Spek A;Wu Y;Giri AK;Yanek LR;Wang L;Hofer E;Rietveld CA;McLeod O;Cornelis MC;Pattaro C;Verweij N;Baumbach C;Abdellaoui A;Warren HR;Vuckovic D;Mei H;Bouchard C;Perry JRB;Cappellani S;Mirza SS;Benton MC;Broeckel U;Medland SE;Lind PA;Malerba G;Drong A;Yengo L;Bielak LF;Zhi D;van der Most PJ;Shriner D;Mägi R;Hemani G;Karaderi T;Wang Z;Liu T;Demuth I;Zhao JH;Meng W;Lataniotis L;van der Laan SW;Bradfield JP;Wood AR;Bonnefond A;Ahluwalia TS;Hall LM;Salvi E;Yazar S;Carstensen L;de Haan HG;Abney M;Afzal U;Allison MA;Amin N;Asselbergs FW;Bakker SJL;Barr RG;Baumeister SE;Benjamin DJ;Bergmann S;Boerwinkle E;Bottinger EP;Campbell A;Chakravarti A;Chan Y;Chanock SJ;Chen C;Chen YI;Collins FS;Connell J;Correa A;Cupples LA;Smith GD;Davies G;Dörr M;Ehret G;Ellis SB;Feenstra B;Feitosa MF;Ford I;Fox CS;Frayling TM;Friedrich N;Geller F;Scotland G;Gillham-Nasenya I;Gottesman O;Graff M;Grodstein F;Gu C;Haley C;Hammond CJ;Harris SE;Harris TB;Hastie ND;Heard-Costa NL;Heikkilä K;Hocking LJ;Homuth G;Hottenga JJ;Huang J;Huffman JE;Hysi PG;Ikram MA;Ingelsson E;Joensuu A;Johansson Å;Jousilahti P;Jukema JW;Kähönen M;Kamatani Y;Kanoni S;Kerr SM;Khan NM;Koellinger P;Koistinen HA;Kooner MK;Kubo M;Kuusisto J;Lahti J;Launer LJ;Lea RA;Lehne B;Lehtimäki T;Liewald DCM;Lind L;Loh M;Lokki ML;London SJ;Loomis SJ;Loukola A;Lu Y;Lumley T;Lundqvist A;Männistö S;Marques-Vidal P;Masciullo C;Matchan A;Mathias RA;Matsuda K;Meigs JB;Meisinger C;Meitinger T;Menni C;Mentch FD;Mihailov E;Milani L;Montasser ME;Montgomery GW;Morrison A;Myers RH;Nadukuru R;Navarro P;Nelis M;Nieminen MS;Nolte IM;O'Connor GT;Ogunniyi A;Padmanabhan S;Palmas WR;Pankow JS;Patarcic I;Pavani F;Peyser PA;Pietilainen K;Poulter N;Prokopenko I;Ralhan S;Redmond P;Rich SS;Rissanen H;Robino A;Rose LM;Rose R;Sala C;Salako B;Salomaa V;Sarin AP;Saxena R;Schmidt H;Scott LJ;Scott WR;Sennblad B;Seshadri S;Sever P;Shrestha S;Smith BH;Smith JA;Soranzo N;Sotoodehnia N;Southam L;Stanton AV;Stathopoulou MG;Strauch K;Strawbridge RJ;Suderman MJ;Tandon N;Tang ST;Taylor KD;Tayo BO;Töglhofer AM;Tomaszewski M;Tšernikova N;Tuomilehto J;Uitterlinden AG;Vaidya D;van Hylckama Vlieg A;van Setten J;Vasankari T;Vedantam S;Vlachopoulou E;Vozzi D;Vuoksimaa E;Waldenberger M;Ware EB;Wentworth-Shields W;Whitfield JB;Wild S;Willemsen G;Yajnik CS;Yao J;Zaza G;Zhu X;Project TBJ;Salem RM;Melbye M;Bisgaard H;Samani NJ;Cusi D;Mackey DA;Cooper RS;Froguel P;Pasterkamp G;Grant SFA;Hakonarson H;Ferrucci L;Scott RA;Morris AD;Palmer CNA;Dedoussis G;Deloukas P;Bertram L;Lindenberger U;Berndt SI;Lindgren CM;Timpson NJ;Tönjes A;Munroe PB;Sørensen TIA;Rotimi CN;Arnett DK;Oldehinkel AJ;Kardia SLR;Balkau B;Gambaro G;Morris AP;Eriksson JG;Wright MJ;Martin NG;Hunt SC;Starr JM;Deary IJ;Griffiths LR;Tiemeier H;Pirastu N;Kaprio J;Wareham NJ;Pérusse L;Wilson JG;Girotto G;Caulfield MJ;Raitakari O;Boomsma DI;Gieger C;van der Harst P;Hicks AA;Kraft P;Sinisalo J;Knekt P;Johannesson M;Magnusson PKE;Hamsten A;Schmidt R;Borecki IB;Vartiainen E;Becker DM;Bharadwaj D;Mohlke KL;Boehnke M;van Duijn CM;Sanghera DK;Teumer A;Zeggini E;Metspalu A;Gasparini P;Ulivi S;Ober C;Toniolo D;Rudan I;Porteous DJ;Ciullo M;Spector TD;Hayward C;Dupuis J;Loos RJF;Wright AF;Chandak GR;Vollenweider P;Shuldiner A;Ridker PM;Rotter JI;Sattar N;Gyllensten U;North KE;Pirastu M;Psaty BM;Weir DR;Laakso M;Gudnason V;Takahashi A;Chambers JC;Kooner JS;Strachan DP;Campbell H;Hirschhorn JN;Perola M;Polašek O;Wilson JF
通讯作者：
Wilson JF
影响因子：
4.5
作者：
Johnson, Emma C.;Evans, Luke M.;Keller, Matthew C.
通讯作者：
Keller, Matthew C.