What do media mogul Oprah Winfrey, actress Mary-Louise Parker, and Olympic runner Carl Lewis have in common? Aside from their more than 15 minutes of fame, all three have been diagnosed with hypothyroidism, a condition where the body does not make enough thyroid hormone. This, in turn, can lead to fatigue, depression, weight gain, and joint pain, among other symptoms. Hypothyroidism affects about 5% of the general population, mostly women over the age of 50, making it the most common thyroid disorder.Hypothyroidism can result from an autoimmune disease such as Hashimoto’s thyroiditis, radiation therapy, or from treatment for hyperthyroidism (overactive thyroid). Genetics are especially likely to play a role in cases with no obvious underlying environmental cause. Despite its prevalence and “celebrity” status, however, the genetic factors influencing hypothyroidism are still mostly unknown.In 2011, the first genome-wide association study of hypothyroidism was published. A year later, 23andMe has published the second, and now largest, study of genetic factors for the condition (read more in our press release). By comparing DNA and survey information from more than 3,700 people with hypothyroidism and about 35,500 people without the condition (all of European descent), we replicated previously observed genetic associations and discovered several additional genetic variants associated with hypothyroidism.Two of these variants are near genes that have already been linked to thyroid disease. The C version of rs925489 near the FOXE1 gene (equivalent to the A version of rs7850258) is associated with slightly lower odds of hypothyroidism and the A version of rs2476601 near the PTPN22 gene is associated with higher odds of the disorder. The PTPN22 variant is actually well-established as a risk factor for multiple autoimmune diseases.A third association is with rs3184504 in the gene SH2B3, which has not been linked to thyroid disease previously but, like PTPN22, is associated with a number of autoimmune conditions. The C version of this SNP is associated with slightly lower odds of hypothyroidism. Similarly, another SNP associated with hypothyroidism in our study, rs2517532, is located in a region of the genome that is important for immune system function.Our findings indicate that there is a significant autoimmune component to hypothyroidism, in addition to influences from genes directly related to thyroid function and hormone levels. Studies have shown that different autoimmune conditions cluster together, suggesting possible shared biology. The association we report between SH2B3 and hypothyroidism is similar to the associations previously reported between this gene and psoriasis, type 1 diabetes, and rheumatoid arthritis, but different from the association between this gene and multiple sclerosis and celiac disease. The placement of hypothyroidism along the spectrum of autoimmune disease may help define future research into causes and treatments for this common disorder.