The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Development of a single-chain peptide agonist of the relaxin-3 receptor using hydrocarbon stapling

Structure activity studies of the insulin super family member, relaxin-3, have shown that its G protein-coupled receptor (RXFP3) binding site is contained within its central B-chain a-helix and this helical structure is essential for receptor activation. We sought to develop a single B-chain mimetic that retained agonist activity. This was achieved by use of solid phase peptide synthesis together with on-resin ruthenium-catalyzed ring closure metathesis of a pair of judiciously placed i,i+4 alpha-methyl, alpha-alkenyl amino acids. The resulting hydrocarbon stapled peptide was shown by solution NMR spectroscopy to mimic the native helical conformation of relaxin-3 and to possess potent RXFP3 receptor binding and activation. Alternative stapling procedures were unsuccessful, highlighting the critical need to carefully consider both the peptide sequence and stapling methodology for optimal outcomes. Our result is the first successful minimization of an insulin-like peptide to a single-chain alpha-helical peptide agonist which will facilitate study of the function of relaxin-3

Associations of autozygosity with a broad range of human phenotypes

436In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.restrictedrestrictedClark D. W.; Okada Y.; Moore K. H. S.; Mason D.; Pirastu N.; Gandin I.; Mattsson H.; Barnes C. L. K.; Lin K.; Zhao J. H.; Deelen P.; Rohde R.; Schurmann C.; Guo X.; Giulianini F.; Zhang W.; Medina-Gomez C.; Karlsson R.; Bao Y.; Bartz T. M.; Baumbach C.; Biino G.; Bixley M. J.; Brumat M.; Chai J. -F.; Corre T.; Cousminer D. L.; Dekker A. M.; Eccles D. A.; van Eijk K. R.; Fuchsberger C.; Gao H.; Germain M.; Gordon S. D.; de Haan H. G.; Harris S. E.; Hofer E.; Huerta-Chagoya A.; Igartua C.; Jansen I. E.; Jia Y.; Kacprowski T.; Karlsson T.; Kleber M. E.; Li S. A.; Li-Gao R.; Mahajan A.; Matsuda K.; Meidtner K.; Meng W.; Montasser M. E.; van der Most P. J.; Munz M.; Nutile T.; Palviainen T.; Prasad G.; Prasad R. B.; Priyanka T. D. S.; Rizzi F.; Salvi E.; Sapkota B. R.; Shriner D.; Skotte L.; Smart M. C.; Smith A. V.; van der Spek A.; Spracklen C. N.; Strawbridge R. J.; Tajuddin S. M.; Trompet S.; Turman C.; Verweij N.; Viberti C.; Wang L.; Warren H. R.; Wootton R. E.; Yanek L. R.; Yao J.; Yousri N. A.; Zhao W.; Adeyemo A. A.; Afaq S.; Aguilar-Salinas C. A.; Akiyama M.; Albert M. L.; Allison M. A.; Alver M.; Aung T.; Azizi F.; Bentley A. R.; Boeing H.; Boerwinkle E.; Borja J. B.; de Borst G. J.; Bottinger E. P.; Broer L.; Campbell H.; Chanock S.; Chee M. -L.; Chen G.; Chen Y. -D. I.; Chen Z.; Chiu Y. -F.; Cocca M.; Collins F. S.; Concas M. P.; Corley J.; Cugliari G.; van Dam R. M.; Damulina A.; Daneshpour M. S.; Day F. R.; Delgado G. E.; Dhana K.; Doney A. S. F.; Dorr M.; Doumatey A. P.; Dzimiri N.; Ebenesersdottir S. S.; Elliott J.; Elliott P.; Ewert R.; Felix J. F.; Fischer K.; Freedman B. I.; Girotto G.; Goel A.; Gogele M.; Goodarzi M. O.; Graff M.; Granot-Hershkovitz E.; Grodstein F.; Guarrera S.; Gudbjartsson D. F.; Guity K.; Gunnarsson B.; Guo Y.; Hagenaars S. P.; Haiman C. A.; Halevy A.; Harris T. B.; Hedayati M.; van Heel D. A.; Hirata M.; Hofer I.; Hsiung C. A.; Huang J.; Hung Y. -J.; Ikram M. A.; Jagadeesan A.; Jousilahti P.; Kamatani Y.; Kanai M.; Kerrison N. D.; Kessler T.; Khaw K. -T.; Khor C. C.; de Kleijn D. P. V.; Koh W. -P.; Kolcic I.; Kraft P.; Kramer B. K.; Kutalik Z.; Kuusisto J.; Langenberg C.; Launer L. J.; Lawlor D. A.; Lee I. -T.; Lee W. -J.; Lerch M. M.; Li L.; Liu J.; Loh M.; London S. J.; Loomis S.; Lu Y.; Luan J.; Magi R.; Manichaikul A. W.; Manunta P.; Masson G.; Matoba N.; Mei X. W.; Meisinger C.; Meitinger T.; Mezzavilla M.; Milani L.; Millwood I. Y.; Momozawa Y.; Moore A.; Morange P. -E.; Moreno-Macias H.; Mori T. A.; Morrison A. C.; Muka T.; Murakami Y.; Murray A. D.; de Mutsert R.; Mychaleckyj J. C.; Nalls M. A.; Nauck M.; Neville M. J.; Nolte I. M.; Ong K. K.; Orozco L.; Padmanabhan S.; Palsson G.; Pankow J. S.; Pattaro C.; Pattie A.; Polasek O.; Poulter N.; Pramstaller P. P.; Quintana-Murci L.; Raikkonen K.; Ralhan S.; Rao D. C.; van Rheenen W.; Rich S. S.; Ridker P. M.; Rietveld C. A.; Robino A.; van Rooij F. J. A.; Ruggiero D.; Saba Y.; Sabanayagam C.; Sabater-Lleal M.; Sala C. F.; Salomaa V.; Sandow K.; Schmidt H.; Scott L. J.; Scott W. R.; Sedaghati-Khayat B.; Sennblad B.; van Setten J.; Sever P. J.; Sheu W. H. -H.; Shi Y.; Shrestha S.; Shukla S. R.; Sigurdsson J. K.; Sikka T. T.; Singh J. R.; Smith B. H.; Stancakova A.; Stanton A.; Starr J. M.; Stefansdottir L.; Straker L.; Sulem P.; Sveinbjornsson G.; Swertz M. A.; Taylor A. M.; Taylor K. D.; Terzikhan N.; Tham Y. -C.; Thorleifsson G.; Thorsteinsdottir U.; Tillander A.; Tracy R. P.; Tusie-Luna T.; Tzoulaki I.; Vaccargiu S.; Vangipurapu J.; Veldink J. H.; Vitart V.; Volker U.; Vuoksimaa E.; Wakil S. M.; Waldenberger M.; Wander G. S.; Wang Y. X.; Wareham N. J.; Wild S.; Yajnik C. S.; Yuan J. -M.; Zeng L.; Zhang L.; Zhou J.; Amin N.; Asselbergs F. W.; Bakker S. J. L.; Becker D. M.; Lehne B.; Bennett D. A.; van den Berg L. H.; Berndt S. I.; Bharadwaj D.; Bielak L. F.; Bochud M.; Boehnke M.; Bouchard C.; Bradfield J. P.; Brody J. A.; Campbell A.; Carmi S.; Caulfield M. J.; Cesarini D.; Chambers J. C.; Chandak G. R.; Cheng C. -Y.; Ciullo M.; Cornelis M.; Cusi D.; Smith G. D.; Deary I. J.; Dorajoo R.; van Duijn C. M.; Ellinghaus D.; Erdmann J.; Eriksson J. G.; Evangelou E.; Evans M. K.; Faul J. D.; Feenstra B.; Feitosa M.; Foisy S.; Franke A.; Friedlander Y.; Gasparini P.; Gieger C.; Gonzalez C.; Goyette P.; Grant S. F. A.; Griffiths L. R.; Groop L.; Gudnason V.; Gyllensten U.; Hakonarson H.; Hamsten A.; van der Harst P.; Heng C. -K.; Hicks A. A.; Hochner H.; Huikuri H.; Hunt S. C.; Jaddoe V. W. V.; De Jager P. L.; Johannesson M.; Johansson A.; Jonas J. B.; Jukema J. W.; Junttila J.; Kaprio J.; Kardia S. L. R.; Karpe F.; Kumari M.; Laakso M.; van der Laan S. W.; Lahti J.; Laudes M.; Lea R. A.; Lieb W.; Lumley T.; Martin N. G.; Marz W.; Matullo G.; McCarthy M. I.; Medland S. E.; Merriman T. R.; Metspalu A.; Meyer B. F.; Mohlke K. L.; Montgomery G. W.; Mook-Kanamori D.; Munroe P. B.; North K. E.; Nyholt D. R.; O'connell J. R.; Ober C.; Oldehinkel A. J.; Palmas W.; Palmer C.; Pasterkamp G. G.; Patin E.; Pennell C. E.; Perusse L.; Peyser P. A.; Pirastu M.; Polderman T. J. C.; Porteous D. J.; Posthuma D.; Psaty B. M.; Rioux J. D.; Rivadeneira F.; Rotimi C.; Rotter J. I.; Rudan I.; Den Ruijter H. M.; Sanghera D. K.; Sattar N.; Schmidt R.; Schulze M. B.; Schunkert H.; Scott R. A.; Shuldiner A. R.; Sim X.; Small N.; Smith J. A.; Sotoodehnia N.; Tai E. -S.; Teumer A.; Timpson N. J.; Toniolo D.; Tregouet D. -A.; Tuomi T.; Vollenweider P.; Wang C. A.; Weir D. R.; Whitfield J. B.; Wijmenga C.; Wong T. -Y.; Wright J.; Yang J.; Yu L.; Zemel B. S.; Zonderman A. B.; Perola M.; Magnusson P. K. E.; Uitterlinden A. G.; Kooner J. S.; Chasman D. I.; Loos R. J. F.; Franceschini N.; Franke L.; Haley C. S.; Hayward C.; Walters R. G.; Perry J. R. B.; Esko T.; Helgason A.; Stefansson K.; Joshi P. K.; Kubo M.; Wilson J. F.Clark, D. W.; Okada, Y.; Moore, K. H. S.; Mason, D.; Pirastu, N.; Gandin, I.; Mattsson, H.; Barnes, C. L. K.; Lin, K.; Zhao, J. H.; Deelen, P.; Rohde, R.; Schurmann, C.; Guo, X.; Giulianini, F.; Zhang, W.; Medina-Gomez, C.; Karlsson, R.; Bao, Y.; Bartz, T. M.; Baumbach, C.; Biino, G.; Bixley, M. J.; Brumat, M.; Chai, J. -F.; Corre, T.; Cousminer, D. L.; Dekker, A. M.; Eccles, D. A.; van Eijk, K. R.; Fuchsberger, C.; Gao, H.; Germain, M.; Gordon, S. D.; de Haan, H. G.; Harris, S. E.; Hofer, E.; Huerta-Chagoya, A.; Igartua, C.; Jansen, I. E.; Jia, Y.; Kacprowski, T.; Karlsson, T.; Kleber, M. E.; Li, S. A.; Li-Gao, R.; Mahajan, A.; Matsuda, K.; Meidtner, K.; Meng, W.; Montasser, M. E.; van der Most, P. J.; Munz, M.; Nutile, T.; Palviainen, T.; Prasad, G.; Prasad, R. B.; Priyanka, T. D. S.; Rizzi, F.; Salvi, E.; Sapkota, B. R.; Shriner, D.; Skotte, L.; Smart, M. C.; Smith, A. V.; van der Spek, A.; Spracklen, C. N.; Strawbridge, R. J.; Tajuddin, S. M.; Trompet, S.; Turman, C.; Verweij, N.; Viberti, C.; Wang, L.; Warren, H. R.; Wootton, R. E.; Yanek, L. R.; Yao, J.; Yousri, N. A.; Zhao, W.; Adeyemo, A. A.; Afaq, S.; Aguilar-Salinas, C. A.; Akiyama, M.; Albert, M. L.; Allison, M. A.; Alver, M.; Aung, T.; Azizi, F.; Bentley, A. R.; Boeing, H.; Boerwinkle, E.; Borja, J. B.; de Borst, G. J.; Bottinger, E. P.; Broer, L.; Campbell, H.; Chanock, S.; Chee, M. -L.; Chen, G.; Chen, Y. -D. I.; Chen, Z.; Chiu, Y. -F.; Cocca, M.; Collins, F. S.; Concas, M. P.; Corley, J.; Cugliari, G.; van Dam, R. M.; Damulina, A.; Daneshpour, M. S.; Day, F. R.; Delgado, G. E.; Dhana, K.; Doney, A. S. F.; Dorr, M.; Doumatey, A. P.; Dzimiri, N.; Ebenesersdottir, S. S.; Elliott, J.; Elliott, P.; Ewert, R.; Felix, J. F.; Fischer, K.; Freedman, B. I.; Girotto, G.; Goel, A.; Gogele, M.; Goodarzi, M. O.; Graff, M.; Granot-Hershkovitz, E.; Grodstein, F.; Guarrera, S.; Gudbjartsson, D. F.; Guity, K.; Gunnarsson, B.; Guo, Y.; Hagenaars, S. P.; Haiman, C. A.; Halevy, A.; Harris, T. B.; Hedayati, M.; van Heel, D. A.; Hirata, M.; Hofer, I.; Hsiung, C. A.; Huang, J.; Hung, Y. -J.; Ikram, M. A.; Jagadeesan, A.; Jousilahti, P.; Kamatani, Y.; Kanai, M.; Kerrison, N. D.; Kessler, T.; Khaw, K. -T.; Khor, C. C.; de Kleijn, D. P. V.; Koh, W. -P.; Kolcic, I.; Kraft, P.; Kramer, B. K.; Kutalik, Z.; Kuusisto, J.; Langenberg, C.; Launer, L. J.; Lawlor, D. A.; Lee, I. -T.; Lee, W. -J.; Lerch, M. M.; Li, L.; Liu, J.; Loh, M.; London, S. J.; Loomis, S.; Lu, Y.; Luan, J.; Magi, R.; Manichaikul, A. W.; Manunta, P.; Masson, G.; Matoba, N.; Mei, X. W.; Meisinger, C.; Meitinger, T.; Mezzavilla, M.; Milani, L.; Millwood, I. Y.; Momozawa, Y.; Moore, A.; Morange, P. -E.; Moreno-Macias, H.; Mori, T. A.; Morrison, A. C.; Muka, T.; Murakami, Y.; Murray, A. D.; de Mutsert, R.; Mychaleckyj, J. C.; Nalls, M. A.; Nauck, M.; Neville, M. J.; Nolte, I. M.; Ong, K. K.; Orozco, L.; Padmanabhan, S.; Palsson, G.; Pankow, J. S.; Pattaro, C.; Pattie, A.; Polasek, O.; Poulter, N.; Pramstaller, P. P.; Quintana-Murci, L.; Raikkonen, K.; Ralhan, S.; Rao, D. C.; van Rheenen, W.; Rich, S. S.; Ridker, P. M.; Rietveld, C. A.; Robino, A.; van Rooij, F. J. A.; Ruggiero, D.; Saba, Y.; Sabanayagam, C.; Sabater-Lleal, M.; Sala, C. F.; Salomaa, V.; Sandow, K.; Schmidt, H.; Scott, L. J.; Scott, W. R.; Sedaghati-Khayat, B.; Sennblad, B.; van Setten, J.; Sever, P. J.; Sheu, W. H. -H.; Shi, Y.; Shrestha, S.; Shukla, S. R.; Sigurdsson, J. K.; Sikka, T. T.; Singh, J. R.; Smith, B. H.; Stancakova, A.; Stanton, A.; Starr, J. M.; Stefansdottir, L.; Straker, L.; Sulem, P.; Sveinbjornsson, G.; Swertz, M. A.; Taylor, A. M.; Taylor, K. D.; Terzikhan, N.; Tham, Y. -C.; Thorleifsson, G.; Thorsteinsdottir, U.; Tillander, A.; Tracy, R. P.; Tusie-Luna, T.; Tzoulaki, I.; Vaccargiu, S.; Vangipurapu, J.; Veldink, J. H.; Vitart, V.; Volker, U.; Vuoksimaa, E.; Wakil, S. M.; Waldenberger, M.; Wander, G. S.; Wang, Y. X.; Wareham, N. J.; Wild, S.; Yajnik, C. S.; Yuan, J. -M.; Zeng, L.; Zhang, L.; Zhou, J.; Amin, N.; Asselbergs, F. W.; Bakker, S. J. L.; Becker, D. M.; Lehne, B.; Bennett, D. A.; van den Berg, L. H.; Berndt, S. I.; Bharadwaj, D.; Bielak, L. F.; Bochud, M.; Boehnke, M.; Bouchard, C.; Bradfield, J. P.; Brody, J. A.; Campbell, A.; Carmi, S.; Caulfield, M. J.; Cesarini, D.; Chambers, J. C.; Chandak, G. R.; Cheng, C. -Y.; Ciullo, M.; Cornelis, M.; Cusi, D.; Smith, G. D.; Deary, I. J.; Dorajoo, R.; van Duijn, C. M.; Ellinghaus, D.; Erdmann, J.; Eriksson, J. G.; Evangelou, E.; Evans, M. K.; Faul, J. D.; Feenstra, B.; Feitosa, M.; Foisy, S.; Franke, A.; Friedlander, Y.; Gasparini, P.; Gieger, C.; Gonzalez, C.; Goyette, P.; Grant, S. F. A.; Griffiths, L. R.; Groop, L.; Gudnason, V.; Gyllensten, U.; Hakonarson, H.; Hamsten, A.; van der Harst, P.; Heng, C. -K.; Hicks, A. A.; Hochner, H.; Huikuri, H.; Hunt, S. C.; Jaddoe, V. W. V.; De Jager, P. L.; Johannesson, M.; Johansson, A.; Jonas, J. B.; Jukema, J. W.; Junttila, J.; Kaprio, J.; Kardia, S. L. R.; Karpe, F.; Kumari, M.; Laakso, M.; van der Laan, S. W.; Lahti, J.; Laudes, M.; Lea, R. A.; Lieb, W.; Lumley, T.; Martin, N. G.; Marz, W.; Matullo, G.; Mccarthy, M. I.; Medland, S. E.; Merriman, T. R.; Metspalu, A.; Meyer, B. F.; Mohlke, K. L.; Montgomery, G. W.; Mook-Kanamori, D.; Munroe, P. B.; North, K. E.; Nyholt, D. R.; O'Connell, J. R.; Ober, C.; Oldehinkel, A. J.; Palmas, W.; Palmer, C.; Pasterkamp, G. G.; Patin, E.; Pennell, C. E.; Perusse, L.; Peyser, P. A.; Pirastu, M.; Polderman, T. J. C.; Porteous, D. J.; Posthuma, D.; Psaty, B. M.; Rioux, J. D.; Rivadeneira, F.; Rotimi, C.; Rotter, J. I.; Rudan, I.; Den Ruijter, H. M.; Sanghera, D. K.; Sattar, N.; Schmidt, R.; Schulze, M. B.; Schunkert, H.; Scott, R. A.; Shuldiner, A. R.; Sim, X.; Small, N.; Smith, J. A.; Sotoodehnia, N.; Tai, E. -S.; Teumer, A.; Timpson, N. J.; Toniolo, D.; Tregouet, D. -A.; Tuomi, T.; Vollenweider, P.; Wang, C. A.; Weir, D. R.; Whitfield, J. B.; Wijmenga, C.; Wong, T. -Y.; Wright, J.; Yang, J.; Yu, L.; Zemel, B. S.; Zonderman, A. B.; Perola, M.; Magnusson, P. K. E.; Uitterlinden, A. G.; Kooner, J. S.; Chasman, D. I.; Loos, R. J. F.; Franceschini, N.; Franke, L.; Haley, C. S.; Hayward, C.; Walters, R. G.; Perry, J. R. B.; Esko, T.; Helgason, A.; Stefansson, K.; Joshi, P. K.; Kubo, M.; Wilson, J. F