Methods of treating metabolic disorders and cardiovascular disease with inhibin subunit beta E (INHBE) inhibitors

A method of treating a subject with a therapeutic agent that treats or inhibits obesity, wherein the subject is suffering from obesity, the method comprising the steps of:

• determining whether the subject has an Inhibin Subunit Beta E (INHBE) variant nucleic acid molecule encoding an INHBE predicted loss-of-function polypeptide by:
• obtaining or having obtained a biological sample from the subject;
• and
• performing or having performed a genotyping assay on the biological sample to determine if the subject has a genotype comprising the INHBE variant nucleic acid molecule;
• and
• when the subject does not have a copy of an INHBE variant nucleic acid molecule encoding an INHBE predicted loss-of-function polypeptide, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits obesity in a standard dosage amount, and/or administering to the subject an INHBE inhibitor;
• and
• when the subject is heterozygous for an INHBE variant nucleic acid molecule, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits obesity in an amount that is the same as or lower than a standard dosage amount, and/or administering to the subject an INHBE inhibitor;
• when the subject is homozygous for an INHBE variant nucleic acid molecule, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits obesity in an amount that is the same as or lower than a standard dosage amount;
• wherein the presence of a genotype having the INHBE variant nucleic acid molecule encoding an INHBE predicted loss-of-function polypeptide indicates the subject has a decreased risk of developing obesity.