Genetic influences are believed to account for 73–93% of the risk of developing the disorder indicating a strong hereditary component. The overall heritability of the bipolar spectrum has been estimated at 0.71. Twin studies have been limited by relatively small sample sizes but have indicated a substantial genetic contribution, as well as environmental influence. For bipolar I disorder, the rate at which identical twins (same genes) will both have bipolar I disorder (concordance) is around 40%, compared to about 5% in fraternal twins. A combination of bipolar I, II, and cyclothymia similarly produced rates of 42% and 11% (identical and fraternal twins, respectively). The rates of bipolar II combinations without bipolar I are lower—bipolar II at 23 and 17%, and bipolar II combining with cyclothymia at 33 and 14%—which may reflect relatively higher genetic heterogeneity.The cause of bipolar disorders overlaps with major depressive disorder. When defining concordance as the co-twins having either bipolar disorder or major depression, then the concordance rate rises to 67% in identical twins and 19% in fraternal twins. The relatively low concordance between fraternal twins brought up together suggests that shared family environmental effects are limited, although the ability to detect them has been limited by small sample sizes. Genetic
Behavioral genetic studies have suggested that many chromosomal regions and candidate genes are related to bipolar disorder susceptibility with each gene exerting a mild to moderate effect.
Endo International plc is an American Irish-domiciled generics and specialty branded pharmaceutical company that generated over 93% of its 2017 sales from the U.S. healthcare system. While Endos management, operations, and customers are almost exclusively U.S.–based, in 2013 Endo executed a corporate tax inversion to Ireland to avoid U.S. corporate taxes on their U.S. drug sales, and to avail of Irelands corporate tax system. History and Acquisitions
Endo was created as a result of a management buyout from DuPont Merck in 1997 led by Carol Ammon.In 2009, Endo bought Indevus Pharmaceuticals to diversify into endocrinology and oncology. The company entered the male hypogonadism market later in 2010 with Fortesta 2% gel. In November 2013, Endo agreed to purchase Paladin Labs Inc for about $1.6 billion to gain access to the Canadian market as well as expand into emerging markets.Endo used the 2013 acquisition of Paladin Labs, and Canadian tax laws, to execute a corporate tax inversion to Ireland. In July 2015, The Wall Street Journal noted Endo was using Irelands lower tax rate to acquire U.S.–based life sciences firms and relocate them to Irelands tax regime (i.e. they could afford to pay more to acquire U.S. competitors).In October 2014, Endo said it would buy Auxilium Pharmaceuticals for $2.6 billion along with its testosterone replacement therapy products.In 2015, Endo acquired the specialty generics and sterile injectables company Par Pharmaceutical for $8.05 billion.In 2018, Endo settled over 1,200 lawsuits related to its testosterone replacement therapy, Testim, and its undisclosed side effects.