@article {469, title = {Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention}, journal = {Nature Genetics}, volume = {54}, year = {2022}, pages = {1332{\textendash}1344}, abstract = {

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

}, doi = {10.1038/s41588-022-01165-1}, author = {Wang, Zhe and Emmerich, Andrew and Pillon, Nicolas J and Moore, Tim and Hemerich, Daiane and Cornelis, Marilyn C and Mazzaferro, Eugenia and Broos, Siacia and Ahluwalia, Tarunveer S and Bartz, Traci M and Bentley, Amy R and Bielak, Lawrence F and Chong, Mike and Chu, Audrey Y and Berry, Diane and Dorajoo, Rajkumar and Dueker, Nicole D and Kasbohm, Elisa and Feenstra, Bjarke and Feitosa, Mary F and Gieger, Christian and Graff, Mariaelisa and Hall, Leanne M and Haller, Toomas and Hartwig, Fernando P and Hillis, David A and Huikari, Ville and Heard-Costa, Nancy and Holzapfel, Christina and Jackson, Anne U and Johansson, \AAsa and J{\o}rgensen, Anja Moltke and Kaakinen, Marika A and Karlsson, Robert and Kerr, Kathleen F and Kim, Boram and Koolhaas, Chantal M and Kutalik, Zoltan and Lagou, Vasiliki and Lind, Penelope A and Lorentzon, Mattias and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Metzendorf, Christoph and Monroe, Kristine R and Pacolet, Alexander and P{\'e}russe, Louis and Pool, Ren{\'e} and Richmond, Rebecca C and Rivera, Natalia V and Robiou-du-Pont, Sebastien and Schraut, Katharina E and Schulz, Christina-Alexandra and Stringham, Heather M and Tanaka, Toshiko and Teumer, Alexander and Turman, Constance and van der Most, Peter J and Vanmunster, Mathias and van Rooij, Frank J A and van Vliet-Ostaptchouk, Jana V and Zhang, Xiaoshuai and Zhao, Jing-Hua and Zhao, Wei and Balkhiyarova, Zhanna and Balslev-Harder, Marie N and Baumeister, Sebastian E and Beilby, John and Blangero, John and Boomsma, Dorret I and Brage, Soren and Braund, Peter S and Brody, Jennifer A and Bruinenberg, Marcel and Ekelund, Ulf and Liu, Ching-Ti and Cole, John W and Collins, Francis S and Cupples, L Adrienne and Esko, T{\~o}nu and Enroth, Stefan and Faul, Jessica D and Fernandez-Rhodes, Lindsay and Fohner, Alison E and Franco, Oscar H and Galesloot, Tessel E and Gordon, Scott D and Grarup, Niels and Hartman, Catharina A and Heiss, Gerardo and Hui, Jennie and Illig, Thomas and Jago, Russell and James, Alan and Joshi, Peter K and Jung, Taeyeong and K{\"a}h{\"o}nen, Mika and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Kolcic, Ivana and Kraft, Peter P and Kuusisto, Johanna and Launer, Lenore J and Li, Aihua and Linneberg, Allan and Luan, Jian{\textquoteright}an and Vidal, Pedro Marques and Medland, Sarah E and Milaneschi, Yuri and Moscati, Arden and Musk, Bill and Nelson, Christopher P and Nolte, Ilja M and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Power, Christine and Raitakari, Olli T and Reedik, M{\"a}gi and Reiner, Alex P and Ridker, Paul M and Rudan, Igor and Ryan, Kathy and Sarzynski, Mark A and Scott, Laura J and Scott, Robert A and Sidney, Stephen and Siggeirsdottir, Kristin and Smith, Albert V and Smith, Jennifer A and Sonestedt, Emily and Str{\o}m, Marin and Tai, E Shyong and Teo, Koon K and Thorand, Barbara and T{\"o}njes, Anke and Tremblay, Angelo and Uitterlinden, Andre G and Vangipurapu, Jagadish and van Schoor, Natasja and V{\"o}lker, Uwe and Willemsen, Gonneke and Williams, Kayleen and Wong, Quenna and Xu, Huichun and Young, Kristin L and Yuan, Jian Min and Zillikens, M Carola and Zonderman, Alan B and Ameur, Adam and Bandinelli, Stefania and Bis, Joshua C and Boehnke, Michael and Bouchard, Claude and Chasman, Daniel I and Smith, George Davey and de Geus, Eco J C and Deldicque, Louise and D{\"o}rr, Marcus and Evans, Michele K and Ferrucci, Luigi and Fornage, Myriam and Fox, Caroline and Garland, Jr, Theodore and Gudnason, Vilmundur and Gyllensten, Ulf and Hansen, Torben and Hayward, Caroline and Horta, Bernardo L and Hypponen, Elina and Jarvelin, Marjo-Riitta and Johnson, W Craig and Kardia, Sharon L R and Kiemeney, Lambertus A and Laakso, Markku and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Marchand, Loic Le and Lifelines Cohort Study and Magnusson, Patrik K E and Martin, Nicholas G and Melbye, Mads and Metspalu, Andres and Meyre, David and North, Kari E and Ohlsson, Claes and Oldehinkel, Albertine J and Orho-Melander, Marju and Pare, Guillaume and Park, Taesung and Pedersen, Oluf and Penninx, Brenda W J H and Pers, Tune H and Polasek, Ozren and Prokopenko, Inga and Rotimi, Charles N and Samani, Nilesh J and Sim, Xueling and Snieder, Harold and S{\o}rensen, Thorkild I A and Spector, Tim D and Timpson, Nicholas J and van Dam, Rob M and van der Velde, Nathalie and van Duijn, Cornelia M and Vollenweider, Peter and V{\"o}lzke, Henry and Voortman, Trudy and Waeber, G{\'e}rard and Wareham, Nicholas J and Weir, David R and Wichmann, Heinz-Erich and Wilson, James F and Hevener, Andrea L and Krook, Anna and Zierath, Juleen R and Thomis, Martine A I and Loos, Ruth J F and Hoed, Marcel den} } @article {440, title = {Identical twins carry a persistent epigenetic signature of early genome programming}, journal = {Nature Communications}, volume = {12}, year = {2021}, pages = {5618}, abstract = {

Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.

}, doi = {10.1038/s41467-021-25583-7}, author = {van Dongen, Jenny and Gordon, Scott D and McRae, Allan F and Odintsova, Veronika V and Mbarek, Hamdi and Breeze, Charles E and Sugden, Karen and Lundgren, Sara and Castillo-Fernandez, Juan E and Hannon, Eilis and Moffitt, Terrie E and Hagenbeek, Fiona A and van Beijsterveldt, Catharina E M and Jan Hottenga, Jouke and Tsai, Pei-Chien and BIOS Consortium and Genetics of DNA Methylation Consortium and Min, Josine L and Hemani, Gibran and Ehli, Erik A and Paul, Franziska and Stern, Claudio D and Heijmans, Bastiaan T and Slagboom, P Eline and Daxinger, Lucia and van der Maarel, Silv{\`e}re M and de Geus, Eco J C and Willemsen, Gonneke and Montgomery, Grant W and Reversade, Bruno and Ollikainen, Miina and Kaprio, Jaakko and Spector, Tim D and Bell, Jordana T and Mill, Jonathan and Caspi, Avshalom and Martin, Nicholas G and Boomsma, Dorret I} } @article {436, title = {Large-scale association analyses identify host factors influencing human gut microbiome composition}, journal = {Nature Genetics}, volume = {53}, year = {2021}, pages = {156{\textendash}165}, abstract = {

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95\% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P \< 5 $\times$ 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 $\times$ 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 $\times$ 10-10 \< P \< 5 $\times$ 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

}, doi = {10.1038/s41588-020-00763-1}, author = {Kurilshikov, Alexander and Medina-Gomez, Carolina and Bacigalupe, Rodrigo and Radjabzadeh, Djawad and Wang, Jun and Demirkan, Ayse and Le Roy, Caroline I and Raygoza Garay, Juan Antonio and Finnicum, Casey T and Liu, Xingrong and Zhernakova, Daria V and Bonder, Marc Jan and Hansen, Tue H and Frost, Fabian and R{\"u}hlemann, Malte C and Turpin, Williams and Moon, Jee-Young and Kim, Han-Na and L{\"u}ll, Kreete and Barkan, Elad and Shah, Shiraz A and Fornage, Myriam and Szopinska-Tokov, Joanna and Wallen, Zachary D and Borisevich, Dmitrii and Agreus, Lars and Andreasson, Anna and Bang, Corinna and Bedrani, Larbi and Bell, Jordana T and Bisgaard, Hans and Boehnke, Michael and Boomsma, Dorret I and Burk, Robert D and Claringbould, Annique and Croitoru, Kenneth and Davies, Gareth E and van Duijn, Cornelia M and Duijts, Liesbeth and Falony, Gwen and Fu, Jingyuan and van der Graaf, Adriaan and Hansen, Torben and Homuth, Georg and Hughes, David A and Ijzerman, Richard G and Jackson, Matthew A and Jaddoe, Vincent W V and Joossens, Marie and J{\o}rgensen, Torben and Keszthelyi, Daniel and Knight, Rob and Laakso, Markku and Laudes, Matthias and Launer, Lenore J and Lieb, Wolfgang and Lusis, Aldons J and Masclee, Ad A M and Moll, Henriette A and Mujagic, Zlatan and Qibin, Qi and Rothschild, Daphna and Shin, Hocheol and S{\o}rensen, S{\o}ren J and Steves, Claire J and Thorsen, Jonathan and Timpson, Nicholas J and Tito, Raul Y and Vieira-Silva, Sara and V{\"o}lker, Uwe and V{\"o}lzke, Henry and V{\~o}sa, Urmo and Wade, Kaitlin H and Walter, Susanna and Watanabe, Kyoko and Weiss, Stefan and Weiss, Frank U and Weissbrod, Omer and Westra, Harm-Jan and Willemsen, Gonneke and Payami, Haydeh and Jonkers, Daisy M A E and Arias Vasquez, Alejandro and de Geus, Eco J C and Meyer, Katie A and Stokholm, Jakob and Segal, Eran and Org, Elin and Wijmenga, Cisca and Kim, Hyung-Lae and Kaplan, Robert C and Spector, Tim D and Uitterlinden, Andre G and Rivadeneira, Fernando and Franke, Andre and Lerch, Markus M and Franke, Lude and Sanna, Serena and D{\textquoteright}Amato, Mauro and Pedersen, Oluf and Paterson, Andrew D and Kraaij, Robert and Raes, Jeroen and Zhernakova, Alexandra} }